In a population-based case-control study in California's intensely agricultural Central Valley (2005-2006), the authors investigated relations between environmental pesticide/fungicide exposure and prostate cancer. Cases (n = 173) were obtained from a population-based cancer registry, and controls (n = 162) were obtained from Medicare listings and tax assessor mailings. Past ambient exposures to pesticides/fungicides were derived from residential history and independently recorded pesticide and land-use data, using a novel geographic information systems approach. In comparison with unexposed persons, increased risks of prostate cancer were observed among persons exposed to compounds which may have prostate-specific biologic effects (methyl bromide (odds ratio = 1.62, 95% confidence interval: 1.02, 2.59) and a group of organochlorines (odds ratio = 1.64, 95% confidence interval: 1.02, 2.63)) but not among those exposed to other compounds that were included as controls (simazine, maneb, and paraquat dichloride). The authors assessed the possibility of selection bias due to less-than-100% enrollment of eligible cases and controls (a critical methodological concern in studies of this kind) and determined that there was little evidence of bias affecting the estimated effect size. This study provides evidence of an association between prostate cancer and ambient pesticide exposures in and around homes in intensely agricultural areas. The associations appear specific to compounds with a plausible biologic role in prostate carcinogenesis.