This paper describes alterations in the incidence of cleft lip and palate in CL/Fr mice subsequent to experimental manipulation of maternal respiratory oxygen levels during a critical period of pregnancy. Only a few previous studies have shown that the incidence of some "genetically determined" malformations in mammals can be decreased by environmental procedures. In addition to demonstrating a decreased incidence of cleft lip and palate subsequent to maternal hyperoxia on gestational days 10 and 11 in a genetically susceptible strain, the results of the present study show that hypoxia at this time increases the incidence of cleft lip and palate.