The pharmacokinetics and metab. of diltiazem (I) was investigated in humans, dogs, rabbits, and rats after each species was given a single oral dose of I. After the drug administration, blood and urine samples were collected for 12 and 48 h, resp. I and six of its metabolites were quantitated by HPLC. The results indicated that, in humans, the major metabolites in plasma were N-monodesmethyldiltiazem (MA), deacetyldiltiazem (M1), and deacetyl-N-monodesmethyldiltiazem (M2). These metabolites were also detected in the plasma of dogs, rabbits, and rats. However, there were quant. differences. For example, in the humans and dogs, MA was the most abundant metabolite in plasma, while M1 and M2 were most prominent in the rabbits and rats, resp., and M2 was a relatively minor metabolite in dog plasma. Less than 5% of the dose was recovered as unchanged I in the urine of all the tested species. The most abundant metabolites and urine appeared to be MA and deacetyl N,O-didesmethyldiltiazem, although there were considerable inter- and intra-species variations. Two addnl. metabolites were detected in the urine of the humans, dogs, and rabbits, but not in the rats. They were tentatively identified as O-desmethyldiltiazem and N-O-didesmethyldiltiazem, using electron impact and ammonia chem. ionization mass spectrometry. Thus, it was concluded that the species differences of I metab. and kinetics were mainly quant. rather than qual.