Dietary fat has been suggested as a risk factor for breast cancer in women, but the available data on humans are sparse and inconsistent. In 1980, 89,538 U.S. registered nurses who were 34 to 59 years of age and had no history of cancer completed a previously validated dietary questionnaire designed to measure individual consumption of total fat, saturated fat, linoleic acid, and cholesterol, as well as other nutrients. In a subsample of 173 participants studied in detail, those in the highest quintile of fat intake consumed a mean of 44 percent of calories from fat, as compared with 32 percent for those in the lowest quintile. During four years of follow-up, 601 cases of breast cancer were diagnosed among the 89,538 nurses in the study. After adjustment for known determinants in multivariate analyses, the relative risk of breast cancer among women in the highest quintile of calorie-adjusted total fat intake, as compared with women in the lowest quintile, was 0.82 (95 percent confidence limits, 0.64 and 1.05). The corresponding relative risks were 0.84 (confidence limits, 0.66 and 1.08) for saturated fat, 0.88 (0.69 and 1.12) for linoleic acid, and 0.91 (0.70 and 1.18) for cholesterol intake. Similar results were found for both postmenopausal and premenopausal women. These data are based on a limited period of follow-up and do not exclude a possible influence of fat intake before adulthood or at levels lower than 30 percent of calories. They suggest, however, that a moderate reduction in fat intake by adult women is unlikely to result in a substantial reduction in the incidence of breast cancer.