Infants with infantile hypertrophic pyloric stenosis (IHPS) born from 1983 to 1988 and recorded in the California Birth Defects Monitoring Program (CBDMP) database were compared with their birth cohort by demographic characteristics and selected associated birth defects. We identified 1963 cases of IHPS for a cumulative incidence of 1.9 per 1000 livebirths. The cumulative incidence per 1000 livebirths was 2.4 in White, 1.8 in Hispanic, 0.7 in Black, and 0.6 in Asian infants. Between weeks 3-12 after birth, 1871 (95%) IHPS cases were diagnosed. Premature infants were diagnosed with IHPS later than term or post-term infants. The incidence of IHPS declined for those born to maternal age groups of > or = 25 years and, independently, for successive birth ranks. The probandwise concordance rate for IHPS in monozygous twins was less than unity (0.25-0.44), although higher than the concordance for dizygous twins (0.05-0.10). The incidence of Smith-Lemli-Opitz syndrome (SLO) diagnosed in infants with IHPS (3 of 1963) was 157-fold higher than the incidence of SLO diagnosed in the CBDMP population. IHPS occurs in all of the largest racial and ethnic groups in California, most frequently in White and Hispanic infants. Pyloric stenosis presents only within a brief phase of development, which may be delayed in premature infants. A predominant discordance of disease state in monozygous twins implies an aetiological role for undetermined environmental factors. The association between SLO, caused by deficient cholesterol synthesis, and IHPS deserves additional study. Infants with suspected SLO require close observation for the onset of IHPS.