The A/WySnBk strain of mice displays 25-35% spontaneous CL(P). Pregnant mice were treated with folinic acid continuously delivered via osmotic minipumps at the rate of 7.6 ฯฎ 0.2 l/ hr (12 mg/ 24 hr) for the period covering gestation day (gd) 8.5-9.5, early in the critical period for formation of the face. Untreated and osmotic minipump-delivered, saline-treated groups served as controls. Individual fetuses were examined for CL(P) and other abnormalities on gd 18. The treatment resulted in a decrease in the frequency of CL(P) from 40.0ฯฎ7.0% among untreated to 10.2ฯฎ3.3% in the folinic acid group (Pฯฝ.001). The difference between the folinic-exposed group and the saline-filled minipump and surgical control was also significant (Pฯฝ.029). With respect to mortality, litter size, and fetal weight, the two minipump groups did not differ significantly, nor did they differ from the untreated group. Thus the reduction in CL(P) frequency was due to the presence of folinic acid and not to effects of the surgical procedures. This study provides evidence that administration of folinic acid during pregnancy has an important ameliorating effect on genetically predis-