To ascertain whether parental involvement in agricultural work and residence in an agricultural setting are associated with the development of congenital limb reduction defects, we carried out a case-control study using California birth records from 1982, 1983, and 1984. Cases with limb reduction defects (N = 237) and randomly selected controls (N = 475) were compared regarding parental occupation and maternal county of residence. After adjustment for potential confounders in a multivariate analysis, the estimated relative risk (RR) of parenting a child with a limb reduction defect among parents involved in agricultural work was 0.9 (95 per cent confidence limits = 0.4, 1.7). The RR among mothers who resided in a county of high agricultural productivity as compared with minimal agricultural productivity was 1.7 (95% CL = 1.1, 2.7), while the RR associated with residence in a county with high pesticide use as compared with minimal pesticide use was 1.9 (95% CL = 1.2, 3.1). When we limited the cases to children with limb reduction defects who had at least one additional anomaly (n = 79) and compared them to the control births, the corresponding RRs were 1.6 (95% CL = 0.7, 3.6), for parental involvement in agricultural work, 2.4 (CL = 1.2, 4.7) for county agricultural productivity, and 3.1 (CL = 1.5, 6.5) for county pesticide use.