Systemic lupus erythematosus characteristically afflicts women of reproductive age, yet the explanation for this feature is unknown. This hospital-based, case-control study of 109 incident cases of systemic lupus erythematosus and 109 randomly selected controls was conducted to search for risk factors related to reproduction. Women who were 34 years of age and younger had a crude risk of systemic lupus erythematosus 3.6 times that of older women, and women who were of minority races had a crude risk 4.8 times that of white women (P less than 0.001). Prior hysterectomy or tubal sterilization had a significant protective effect (odds ratio, 0.55; 95% confidence interval, 0.31 to 0.99). Endometriosis was associated with a twofold increased risk of systemic lupus erythematosus, although this was not statistically significant. The latter two findings are consistent with the hypothesis that retrograde menstruation may be an inciting factor for systemic lupus erythematosus in susceptible women.