Experimenters in toxicology often compare the concentration‐response relationship between two distinct populations using the median lethal concentration (LC50). This comparison is sometimes done by calculating the 95% confidence interval for the LC50 for each population, concluding that no significant difference exists if the two confidence intervals overlap. A more appropriate test compares the ratio of the LC50s to 1 or the log(LC50 ratio) to 0. In this ratio test, we conclude that no difference exists in LC50s if the confidence interval for the ratio of the LC50s contains 1 or the confidence interval for the log(LC50 ratio) contains 0. A Monte Carlo simulation study was conducted to compare the confidence interval overlap test to the ratio test. The confidence interval overlap test performs substantially below the nominal α = 0.05 level, closer to p = 0.005; therefore, it has considerably less power for detecting true differences compared to the ratio test. The ratio‐based method exhibited better type I error rates and superior power properties in comparison to the confidence interval overlap test. Thus, a ratio‐based statistical procedure is preferred to using simple overlap of two independently derived confidence intervals.