B group vitamins including folic acid supplementation during pregnancy have been shown to be effective in preventing cleft lip and palate (CLP) in humans. The clinical trials for the prevention of malformation have been mostly empirically based. The aim of the present study was directed toward the elucidation of the mechanisms underlying the preventive measures. The teratogenic potency of vitamin deficiency over the whole period of gestation (days 1-18) and of food restriction during the critical period of palatogenesis (days 12 and 13) were investigated in the genetically different strains of NMRI and A/WySn mice. Furthermore the potential benefit of vitamin B supplementation/treatment in the genetically susceptible CLP strain was demonstrated for comparison with former work on a teratogenetically induced cleft palate model. The results illustrate the higher susceptibility of the NMRI strain to the teratogenic action of deficiency (increase of the CP rate from 3.8% to 25%) in contrast to A/WySn mice, which actually have a high spontaneous but relative teratogenic-resistant clefting rate (28-44%). A deficiency of each of the individual B vitamins is teratogenic, however total B group deficiency has the strongest effect in the case of deficiency of all B vitamins. This produces up to 25% cleft palates in the NMRI strain. Alternatively, vitamin B group treatment in pregnant A/WySn mice did not substantially influence the clefting rate in contrast to our former experience in Halle:AB mice. The results may help to elucidate the interplay of genetic conditions and exogenous (nutritional) factors in both the aetiology and prevention of CLP. This may further clarify the role of the B vitamins in empiric preventive clinical trials.