The authors examined the relation of constitutional factors and sun exposure to risk of basal cell carcinoma of the skin (BCC) in a prospective cohort of 44,591 predominantly Caucasian US male health professionals, 40-75 years of age and free of cancer at enrollment in 1986. During 8 years of follow-up, 3,273 cases of self-reported BCC were documented. The following variables were each associated with an elevated risk of BCC: having red hair; green, hazel, or blue eyes; a tendency to sunburn; and north European ancestry. The lifetime number of blistering sunburns was also positively associated with BCC risk (p trend < 0.0001). Compared with men who as teenagers had been outside less than once a week, men who had been outside weekly (relative risk (RR) = 1.30; 95% confidence interval (CI): 1.14, 1.47) and daily (RR = 1.42; 95% CI: 1.24, 1.63) had an elevated risk of BCC. Living in a region of residence with high solar radiation as an adult was also associated with an increased risk of BCC (RR = 1.48; 95% CI: 1.36, 1.60), whereas living in such a region only in childhood did not increase BCC risk. These results confirm the role of constitutional factors and suggest that adult sun exposure increases BCC risk.