Tiodazosin is a recently developed compound that is currently undergoing investigation for use in hypertension. It is structurally and pharmacologically similar to prazosin, the prototype of the aminoquinazoline class of vasodilators. Lacking an intravenous dosage form for use in human subjects, our study concentrated on the determination of the bioavailability and disposition parameters of tiodazosin in dogs, with a comparison to those parameters for prazosin, obtained from previous work in our laboratory. Tiodazosin was administered to five male beagle dogs at a dose of 1 mg/kg both intravenously and as an oral solution. Plasma and whole blood samples were taken serially over 24 hr and analyzed with a new specific and sensitive HPLC assay. The half-life of tiodazosin was significantly shorter than that of prazosin. The tiodazosin-calculated bioavailability was 3-fold less than predicted, whereas prazosin-calculated bioavailability was the same as predicted. Assumptions necessary to predict the bioavailability of compounds cleared by the hepatic route appear to be incorrect for tiodazosin. Possible mechanisms for the unpredictable low tiodazosin bioavailability in dogs are presented.