Background: Mutations in the ataxia-telangiectasia (A-T) gene cause an autosomal recessive syndrome in homozygotes and compound heterozygotes and predispose female heterozygous carriers to breast cancer. No environmental agent has been previously shown to increase the risk of cancer for women who carry a mutated gene that predisposes to breast cancer. This study assesses the effect of cigarette smoking on the risk of breast cancer in A-T mutation carriers and determines age-specific and cumulative incidence rates for breast cancer among such carriers. Methods: Clinical data were collected between 1971 and 1999 from blood relatives from 274 families of patients with A-T. The A-T mutation carrier status of 973 females was determined by molecular analysis of blood and tissue samples. The breast cancer rates in carrier smokers and nonsmokers were compared. Age-specific