Objective: To investigate whether periconceptional maternal alcohol consumption increased the risk of delivering infants with orofacial cleft phenotypes. Design: Data were derived from a large population-based case control study of fetuses and infants among a cohort of California births from 1987 to 1989 (n = 548,844). Information concerning alcohol consumption was obtained by telephone interviews with mothers of 731 infants (84.7% of eligible) with orofacial clefts and of 734 (78.2%) infants in a nonmalformed control group. Results: Thirty-nine percent of mothers in the case group and 42% of mothers in the control group reported that they consumed alcohol during the period 1 month before through 3 months after conception. Relative to nonconsumers, women who reported alcohol consumption (<weekly, weekly, or daily) were not at substantially increased risk of delivering infants with any cleft phenotype. However, for women who reported weekly or more frequent episodes of consuming ≥5 drinks per drinking occasion compared with those who did not, we observed increased risks for isolated (no other major congenital anomaly) cleft lip with or without cleft palate, odds ratio = 3.4 (95% confidence interval, 1.1 to 9.7); multiple cleft lip with or without cleft palate, odds ratio = 4.6 (1.2 to 18.8); and “known syndrome” clefts, odds ratio = 6.9 (1.9 to 28.6). Adjustment for maternal cigarette smoking, race, education, or vitamin use did not substantially change observed risks. Conclusion: We observed a lack of increased risks of clefts for relatively low quantities of maternal alcohol consumption and increased risks of clefts for higher quantities of maternal alcohol consumption. (J Pediatr 1999;134:298-303)