A high total number of full-term pregnancies is associated with a reduced risk of breast cancer, though pregnancy transiently increases the risk of the disease. However, little attention has been given to a possible association of breast cancer risk with the gender of offspring, even though male fetuses have been associated with several factors linked to a low breast cancer risk, namely, pregnancy toxemia, increased levels of β£-fetoprotein (AFP) and increased levels of sex hormone-binding globulin. We used data from linked Swedish registries to study the relative importance of male and female offspring as risk correlates of subsequent breast cancer in the mothers. In a nested case-control study, case patients were 2,328 women who had one or more live-born children delivered between 1973 and 1989 and who were subsequently diagnosed with breast cancer during this period. For comparison, 10,256 control subjects, matched to cases by birth year, were randomly selected from among the eligible women. Number of boys was inversely associated and number of girls positively associated with breast cancer risk. Neither of these trends was significantly different from the null value, but the difference between the 2 trends was marginally significant ( p β«Ψβ¬ 0.06). Moreover, women who gave birth to 2 or more boys but no girls were at significantly lower risk for breast cancer in comparison to women who gave birth to 2 or more girls but no boys; the odds ratio was 0.78 (95% CI 0.64-0.95). The apparently protective effect of pregnancies with male fetuses was limited to women younger than 40 years. Endocrine or other metabolic processes specifically associated with a male rather than a female fetus may impart relative protection against the occurrence of breast cancer during the childbearing period.