The joint action of all-trans retinoic acid (RA) with valproic acid (VPA) was examined at malformation-inducing concentrations for Xenopus embryos. The compounds were selected for testing to evaluate malformation as an endpoint for the developmental toxicity of chemical mixtures and to help assess whether joint action types can be related to modes or mechanisms of chemical toxicity for Xenopus. Three mixtures (3:1, 1:1, and 1:3 RA:VPA) were tested in 96 hr static-renewal exposures. Three separate tests were conducted on each mixture. Positive controls were also tested (i.e., 1:0 and 0:1 solutions). Using toxic unit analysis, the joint action for induction of malformations of all types, craniofacial malformations, and microcephaly was response addition, indicating the chemicals are dissimilar and non-interactive. The results support recent joint action studies in providing evidence that similar acting chemicals might be defined as chemicals with the same biochemical/molecular mechanism of action in inducing malformations in Xenopus embryos. © 1992 Wiley-Liss, Inc.