The segregation pattern of breast cancer in white families from the Cancer and Steroid Hormone Study was investigated. Families were categorized into four groups based on the histologic type of breast cancer in the probands:ductal cancer, lobular cancer, adenocarcinoma, and medullary cancer. The ductal cancer sample was further split into a premenopausal-proband and a postmenopausal-proband subset. Results for six complex segregation analyses are presented; the findings suggest heterogeneity in the transmission of breast cancer. For all analyses, there was no evidence for a multifactorial component in the mixed model, ie, a major locus plus other transmission, genetic and/or cultural. Interpretation of the medullary cancer, adenocarcinoma, and lobular cancer analyses does not permit discrimination among the major locus models. Segregation of breast cancer in the entire ductal sample was consistent with autosomal recessive transmission. In the ductal subanalyses, a recessive gene was sufficient to explain the breast cancer distribution when the proband had postmenopausal breast cancer. In contrast, when the proband had premenopausal breast cancer, the transmission model was consistent with a dominant major gene, with sporadic cases of disease.