Pharmacokinetics of verapamil and of its three primary metabolites [norverapamil, 2-(3,4-dimethoxyphenyl)-2-isopropyl-6-azaheptanitrile (D-617) and 2-(3,4-dimethoxyphenyl)-2-propylamino-3-methylbutyronitrile (D-260)] was studied after oral administration in 7 patients with stable angina pectoris. Serum levels of metabolites were found to be in the same range as that of the intact drug. Areas under the serum concentration time curves of each metabolite were higher and serum half-lives were significantly longer than those of verapamil. Half-life values obtained from urinary excretion data and from serum levels did not differ for the metabolites, but for the unchanged drug, the half-life from urinary excretion data was longer. Cumulative urinary excretion of verapamil, norverapamil, D-617 and D-620 up to 48 h postdose was averaged to 1%, 2.2%, 11.4%, and 6.7% of the dose administered, respectively. The extent of verapamil bioavailability was directly measured in one patient receiving an intravenous dose as well as an oral one and was found to be 42.3%. In other patients, bioavailability was assessed by means of a regression equation relating the reciprocal of bioavailability and oral clearance of the drug, and was averaged at 35.1%. The possibilities of contribution of the metabolites to verapamil effects in patients were discussed.