Met•Enk is a naturally occurring opioid pentapeptide (Try-Gly-Gly-Phe-Met) that may be involved with intercellular communication in the nervous, endocrine, and immune systems. Because of potential therapeutic utility of this peptide, subchronic intravenous toxicity studies were performed in rats (28 days) and dogs (27 days). Met-Enk was administered intravenously at dosages of 1.25, 6.25, and 25 mg/kg at rates of 2 ml/min (rat) and 2-4 ml/min (dog). Treatment groups were compared on the basis of survival, overt signs of toxicity, body weight gain, changes in organ weights, ophthalmological assessment, urinalysis, hematological and clinical chemistry profiles, and gross and microscopic tissue changes. No lethalities occurred in either species. Clinical signs observed only in dogs treated with Met-Enk included emesis, excessive salivation, diarrhea and apparent hyperphagia in all dosage groups. Relaxation of the nictitating membrane also occurred, preponderately in the higher dosage groups. No toxicologically significant findings were evident in any of the clinical pathology parameters evaluated or in the gross or microscopic tissue assessments of either species.