The authors examined the association between the use of diethylstilbestrol during pregnancy and the risk of subsequent fatal breast cancer in a large prospective study of US adults. After 9 years of follow-up, 1,574 cases of fatal breast cancer were observed among 501,536 gravid women who reported no prior history of cancer in 1982. Results from Cox proportional hazards models showed a positive association between a history of diethylstilbestrol exposure (reported by 3.9% of all women) and fatal breast cancer (adjusted rate ratio = 1.34, 95% confidence interval 1.06-1.69). This excess risk did not increase over time; women who were exposed more than 35 years ago (rate ratio = 1.35, 95% confidence interval 0.97-1.87) were not at greater risk than women who were exposed within the past 35 years (rate ratio = 1.39, 95% confidence interval 1.01-1.93). The positive association was not observed in women who used diethylstilbestrol before age 25 years but was seen at all other ages. The age of study participants did not modify the association between exposure and breast cancer, and there were no significant interactions between ever use of diethylstilbestrol and any of the other potential risk factors included in the analysis. These findings are consistent with those of several other studies of diethylstilbestrol exposure and breast cancer.