Hydroxyprogesterone caproate (17-OHPC) is used to prevent preterm labor in pregnant subjects. In the present study inter-species difference in the metabolism of 17-OHPC was evaluated using liver microsomes from mouse, rat, rabbit, pig, dog and baboon and compared with human liver microsomes and primary human hepatocyte cultures. In all the species evaluated, monohydroxylated 17-OHPC was observed to be the major metabolite. Significant inter-species difference in the rate of 17-OHPC metabolism was observed both qualitatively and quantitatively. Ketoconazole inhibited 17-OHPC metabolism in all the species evaluated confirming the dominant role of CYP3A (rats, rabbits, dog, pig, dog, baboon) and cyp3a (mice) in the metabolic pathway. It is concluded that monohydroxylated 17-OHPC is the major metabolite of 17-OHPC in various animal species. The baboon seems to provide the most suitable model for evaluating the pharmacokinetics of 17-OHPC in animals and screening for potential drug-drug interactions although interspecies variation exists in the disposition of 17-OHPC.