Following intraperitoneal administration to rats of [14C]loperamide, [carbonyl-14] 4-(p-chlorophenyl)-4-hydroxy-N,N-dimethyl-alpha, alpha-diphenyl-1-piperidine butyramide, metabolites in feces and urine were separated, and identified by means of mass spectrometry. In feces, six metabolites were identified in addition to the unchanged drug. The main metabolic pathways involved are dealkylation in the dimethyl amide moiety to give desmethyl- and didesmethylloperamide, both of which were in turn monohydroxylated either in the alpha-phenyl ring or possibly in the alpha-carbon in the piperidine ring. It is noteworthy that metabolites hydroxylated in the piperidine ring were isolated as pyridinium derivatives, possibly due to spontaneous aromatization of its 2,4-dihydroxy-4-(p-chlorophenyl)piperidine ring. In urine, only two metabolites were found and identified to be desmethyl- and didesmethylloperamide, since [14C]loperamide was excreted into urine only in a small amount.