Abstract5,5‐Diphenylhydantoin (DPH) is an antiepileptic drug associated with an increase in malformations in infants born to women taking DPH during pregnancy. Positive and negative results have been reported by various investigators for in vivo and in vitro chromosome aberration (CAB) assays, in vivo and in vitro sister chromatid exchange (SCE) assays, and in vivo micronucleus tests (MNT). In this laboratory, DPH was tested in an in vitro CAB assay using Chinese hamster ovary cells with and wihout an S‐9 activation system, an in vivo SCE assay in female CD‐1 mice, an in vivo MNT, using both male and female CD‐1 mice, and a transplacental micronucleus test. The results from this comprehensive battery of cytogenetic tests were uniformly negative and support a conclusion that the known teratogen, DPH, is not clastogenic. © 1992 Wiley