To determine whether the hydroxylation of 5,5-diphenylhydantoin (DPH) [an antiepileptic agent] to 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) occurs by an arene oxide-NIH shift process, (.+-.)-5-(4-deuteriophenyl)-5-phenylhydantoin (p-2H-DPH) was subjected to in vivo metabolic experiments in the rat and in man. After enzymatic hydrolysis of the urine, p-hydroxylated metabolites were separated by HPLO [high performance liquid chromatograhph]. Deuterium retention in the isolated metabolites, determined by gas chromatography-mass spectrometry, was 68-72%. An arene oxide-NIH shift pathway predominates in those 2 metabolic systems. Induction of rats with phenobarbital or 3-methylcholanthrene showed no effect on the value of deuterium retention.