The human urinary metabolites of diltiazem [a coronary vasodilator] were analyzed by TLC and gas chromatography-mass spectrometry. Diltiazem was metabolized by deacetylation, N-demethylation, O-demethylation and conjugation. Metabolite MA, N-monodemethyl-diltiazem, was identified as a new major metabolite in human urine, and 4 metabolites were identified as deacetyl-diltiazem (M1), deacetyl-N-monodemethyl-diltiazem (M2), deacetyl-O-demethyl-diltiazem (M4) and deacetyl-N,O-demethyl-diltiazem (M6) which were known as rat urinary metabolites. Metabolite M2, M4 and M6 were converted in part to glucuronides and/or sulfates. Unchanged diltiazem and metabolite MA were determined in human plasma and urine by TLC-densitometry. Diltiazem and metabolite MA excreted in 24 h urine were 44.4 and 48.5% of the total unconjugated form, respectively. The mean plasma level of metabolite MA was approximately 1/3 of diltiazem level. On the basis of these findings, a probable metabolic pathway of diltiazem in man is presented.