Mice used to model induction of cleft palate and kidney malformations in offspring following maternal treatment with TCDD, were dosed on gestation day with hexachlorobiphenyl (HCB) and/or with tetrachlorodibenzo-p-dioxin (TCDD) to investigate the potential protective effects of HCB against TCDD-induced teratogenicity. At the doses used in the study, there was no effect of either compound on number of live or dead offspring. Fetal body weight was slightly decreased in all groups dosed with = or > 250 mg HCB/kg. HCB did not induce cleft palate at a dose of 1000 mg/kg, but did induce increases in hydronephrosis and hydroureter at 500 and 1000 mg/kg. Combinations of HCB and TCDD decreased the incidence of cleft palate induced by TCDD alone, but only at doses of 15 microgram TCDD/kg combined with 125-500 mg HCB/kg. The window for antagonism of hydronephrosis (incidence and severity) appeared narrower (15 microgram TCDD/kg + 500 mg HCB/kg). HCB induced increases (3 fold) in EROD activity at doses of 500 and 1000 mg/kg, suggesting that the limited antagonism of TCDD teratogenicity by HCB would be consistent with control by Ah receptor. (Copyright (c) 1992 Elsevier Science Publishers B.V.)