Background and Purpose: Acute inhalation exposure to nickel has been shown to cause immune and respiratory effects in animal and occupational epidemiologic studies. Several state air toxics control programs, including those of Minnesota, Texas and Oregon, assess potential hazards for peak 24-hour exposures to protect against acute effects. However, federal sources for acute standards use differing definitions of acute exposure. For example, the Agency for Toxic Substances and Disease Registry (ATSDR) acute inhalation Minimum Risk Level (MRL) is for exposures of 1 to 14 days, and the US Environmental Protection Agency (EPA) and National Research Council Acute Guideline Exposure Levels are for exposures up to 8-hours in duration. As a result, state agencies have taken a variety of approaches to develop acute values for specific exposure durations, including adopting federal values regardless of a common definition of ‘acute’, adjusting the exposure durations to meet the needs of their programs, and/or developing state-specific values, resulting in considerable inconsistency. For nickel, the federal and state acute inhalation reference values vary by more than 100-fold. Methods: The nickel acute RfC was derived by 1) reviewing data from authoritative sources and the scientific literature to determine sensitive Points of Departure (PODs), 2) developing and applying dose adjustment factors (DAFs) to account for differences in dosimetry between animals and humans, 3) applying time adjustment factors to calculate Human Equivalent Concentrations (HECs), and 4) applying appropriate uncertainty factors. Because the ATSDR (2024) recently concluded that the most sensitive endpoints for acute nickel exposure were immunotoxicity and respiratory irritation, our literature review focused on these endpoints. Authoritative sources for acute toxicity data for nickel included the ATSDR, EPA, Texas Commission on Environmental Quality (TCEQ), and California Office of Environmental Health Hazard Assessment (OEHHA). To determine the most sensitive POD, benchmark concentrations (BMCs) and LOAECs and NOAECs from the scientific literature were compared. To calculate the DAF, the multiple-path particle dosimetry (MPPD) model was run to estimate an HEC. Results: The literature review supported that immune effects are the most sensitive endpoint for acute exposures to nickel. Efremenko et al. (2017) evaluated transcriptomic responses to Ni inhalation exposure for 6 hours/ day, 5 days/week for 1 and 4 weeks and found that the lowest BMCs were observed for immune responses (0.047 mgNi/m3). The POD for acute immunosuppressive response was the NOAEC of 0.081 mg Ni/m3 reported by Buxton et al. (2021) in mice administered nickel chloride for 24 hours and challenged with sheep Red Blood Cells. Buxton et al. (2021) followed the Office of Prevention, Pesticides and Toxic Substances (OPPTS) guideline #870.7800 for immunotoxicity and was good laboratory practice-(GLP-) compliant. To calculate the DAF, the MPPD model was run for the mouse and the human. MPPD only has two options for a mouse model species (BALB/c and B6C3F1); however, CD-1 mice were used in the Buxton et al. (2021) study. Thus, model runs were made with assumptions for each mouse species for comparison. Most input parameters are automatically calculated in the MPPD model. The resulting HECs ranged from 0.279 to 0.439 mg/m3, with a median value of 0.318 mg/m3. Using the median value as the PODHEC and a 30-fold uncertainty factor (ten for intraspecies sensitivity and three for interspecies kinetic variability) results in an acute RfC of 11 μg/m3 which is similar to that derived by the Minnesota Pollution Control Agency. Conclusions: The transcriptomic BMD at one week of exposure for immune effects is considerably lower than the LOAEC for respiratory effects as reported in Efremenko et al. (220 μg/ m3) which was used by ATSDR as the basis for the acute MRL. The acute RfC of 11 μg/m3 is also supported by the transcriptomic BMCs (47 μg/m3). Further, because it is based on a Guideline and GLP study, and provides a NOAEC for 24-hour exposures, the 11 μg/m3 acute RfC developed herein is less uncertain than values developed from other studies, including those reporting respiratory effects.