In a prospective study of self-reported demographic, constitutional, and life-style factors in relation to basal cell carcinoma of the skin, we followed a cohort of 73,366 nurses in the United States who were 34 to 59 years of age in 1980 and who had no previous skin or other cancer. In 4 years of follow-up, compared with women living in the Northeast, women residing in California (age-adjusted relative risk [RR] = 1.57; 95% confidence interval [CI] = 1.30 to 1.89) and Florida (RR = 2.12; 95% CI = 1.54 to 2.92) were more likely to develop basal cell carcinoma. Compared with women having naturally dark brown hair, the age-adjusted relative risk of basal cell carcinoma was increased among women with red (RR = 2.45; 95% CI = 1.89 to 3.19), blonde (RR = 1.37; 95% CI = 1.09 to 1.71), or light brown hair (RR = 1.27; 95% CI = 1.08 to 1.49) and was decreased among women with black hair (RR = 0.66; 95% CI = 0.41 to 1.06). Risk was positively associated in a dose-response manner both with tendency to sunburn as a child or adolescent and with lifetime number of severe and painful sunburns on the face or arms. These risk factors remained significant predictors of disease when included simultaneously in multivariate analyses. Tendency to tan was associated with decreased risk, although this risk was not significant after controlling for the other constitutional determinants and region. Cigarette smoking did not alter the risk of basal cell carcinoma. These prospective data emphasize the importance of sunlight, and skin response to sunlight, as determinants of basal cell carcinoma among women.