The pharmacokinetics and bioavailability of domperidone, a novel gastrokinetic, were studied in healthy male subjects by comparing plasma concentrations and urinary excretion following intravenous, intramuscular, oral and rectal administration. Two oral dosage forms were studied: 10-mg tablets and a 10-mg/ml oral solution. The influence of a meal on the oral bioavailability and the dose-proportionality were also investigated. Plasma levels of intravenous domperidone could be described by a three-compartment model with a rapid distribution of 40% of the dose to a "shallow" peripheral compartment. The final elimination half-life was 7.5 hours. Peak plasma levels were reached within 30 minutes following intramuscular and oral administration and at 1-4 hours following rectal administration. Since domperidone showed an extensive first-pass elimination, AUC-values -a measure for the bioavailability- were considerably lower after oral than after parenteral administration. Equal oral and rectal doses gave a similar bioavailability. AUC-values increased proportionally with the dose over a 10-60 mg range. Cumulative urinary excretion of unchanged domperidone was proportional to corresponding AUC-values. The bioavailability was discussed in the light of the therapeutic results.