The kinetics of the antiplatelet drug dipyridamole were studied in six normal subjects (three men and three women) who were ages 22 to 34 yr old. Each received 20 mg IV and four also took a 50-mg oral dose. Blood samples were collected after each dose for a period of 3 days and concentrations of dipyridamole were measured by a sensitive and specific high-performance liquid chromatographic assay. Concentrations after the intravenous dose showed a triexponential decline with a terminal half-life of 11.6 +/- 2.2 hr (x +/- SD). Total plasma clearance was 8.27 +/- 1.82 1/hr and the apparent volume of distribution was 141 +/- 51 1. Concentrations rose 6 to 10 hr after intravenous dipyridamole in each female subject, but not in the male subjects. Dipyridamole blood/plasma concentration ratio changed from an average of 0.7 over the first hour to 1.2 after 5 hr after the intravenous dose. There was an absorption lag time ranging from 34 to 75 min after the oral dose; concentrations peaked at about 2 to 2.5 hr after the dose. The percentage of unbound drag in plasma was 0.88 +/- 0.24%. Systemic availability of the end oral dose was 43 +/- 13%. These results suggest widely varying concentrations in patients receiving the drug, and raise questions about the current clinical practice of using empirical dosage schedules.