Metabolism of the hypoglycemic agent, pirogliride, was investigated in the rat, dog monkey and human. Unchanged pirogliride plus six metabolites were isolated and identified using solvent extraction, HPLC and CI and EI-MS from urine and fecal samples. Pirogliride was metabolized in man to a small extent by oxidation of the 4-position of the phenyl ring. The monkey metabolized pirogliride mainly by oxidation of the pyrrolidine rings, while oxidation of the phenyl ring was the minor pathway. In contrast to the monkey, the rat metabolized pirogliride primarily by oxidation of the phenyl ring. The dog showed a balance of oxidation between the phenyl and pyrrolidine rings.