The inhibition by hydralazine of the clorgyline-resistant amine oxidase (CRAO) and monoamine oxidase (MAO) activities in various rat tissues has been studied. Hydralazine was a potent, time-dependent inhibitor of rat heart CRAO activity in vitro. The inhibition was not reversed by dialysis for 18 hr at 4 degrees, and only partially reversed by dialysis at 37 degrees. Dialysis at 4 degrees in the presence of pyridoxal phosphate (10(-4) M) also did not reverse the inhibition. Ex vivo inhibition of CRAO was found in heart and aorta homogenates in a dose-dependent manner after administration of hydralazine (1-40 mg/kg i.p.) to rats. In contrast, MAO-A activity was unaffected or, in some cases, significantly increased in these tissue homogenates from drug-treated animals. However, in vitro inhibition by hydralazine of both MAO-A and B activities of rat liver mitochondrial fractions was found, and these effects were fully reversible by dialysis for 18 hr at 4 degrees. Inhibition of MAO-A was competitive (Ki of 2.5 X 10(-6) M), while inhibition of MAO-B showed complex mixed non-competitive kinetics. These results indicate that hydralazine possesses different inhibitory properties towards the various amine oxidases in rat tissues, and these actions are discussed in relation to the clinical use of the drug as an anti-hypertensive agent.