This study investigated whether the current range in dietary fat levels, which has arisen partly in response to some major health concerns, would affect frequency of congenital anomalies if continued into the period of early pregnancy. The effect of 5.6%, or 48% of calories from fat in the maternal diet, was tested on pregnant strain CD-1 mice injected with triamcinolone in doses of 0.01 mg, 0.02 mg, 0.04 mg, or 0.06 mg per day on days 11 through 14 of gestation. Frequency of cleft palate increased with increasing doses of triamcinolone, with clefts of the palate being rare at the two lower doses. No clefts appeared without triamcinolone on either diet. In combination with triamcinolone treatment, 226 fetuses exposed to a maternal low fat diet had normal palates and 86 had cleft palates. With exposure to high fat, 186 fetuses had normal palates and 101 had cleft palates, which was a significant increase in clefting (p < 0.05). Also, the latter group showed a greater degree of retardation in palate development (p < 0.05). Thus both a greater frequency and a more severe form of clefting support the conclusion that high dietary fat potentiated the cleft palate-producing effects of triamcinolone in mice.