We investigated the relationship of body size and prostate cancer risk in the Multiethnic Cohort, a longitudinal study of individuals ages 45 to 75 in Hawaii and in California. Self-reported measures of height and weight were obtained at baseline. Of 83,879 men enrolled from 1993 to 1996, a total of 5,554 were diagnosed with prostate cancer during an average of 9.6 years of follow-up. The influence of baseline weight and weight change since age 21 varied by ethnic group. Whites gaining more than 10 lbs had a nonlinear, increased risk of advanced and high-grade prostate cancer [relative risks (RR), 2.12; 95% confidence intervals (CI), 1.19-3.78 for 25-39.9 lbs; P trend 0.43; and RR, 1.49; 95% CI, 1.04-2.14, for >or=40 lbs; P trend 0.20, respectively]. African American men gaining 40 lbs or more (relative to <10 lbs) had a nonmonotonic, increased risk of localized prostate cancers (RR, 1.26; 95% CI, 1.02-1.54; P trend 0.09) and those who gained 25 lbs or more were at increased risk of low-grade disease (RR, 1.28; 95% CI, 1.03-1.58, for >or=40 versus 10 lbs, respectively; P trend 0.07). Japanese men had a statistically significant, inverse association of weight gain and localized disease (RR, 0.80; 95% CI, 0.65-0.99 for >or=40 versus 10 lbs; P trend 0.05). Our findings provide evidence that adiposity and changes in adiposity between younger and older adulthood influence the development of prostate cancer. Ethnic differences in risk may be explained by variation in the distribution of accumulated body fat that could differentially affect prostate carcinogenesis.