Several recent studies have suggested a potential role of menstrual and reproductive factors in the risk of non-Hodgkin's lymphoma. To further examine the relation, the authors analyzed data from a population-based case-control study of non-Hodgkin's lymphoma in Connecticut women between 1996 and 2000. A total of 601 histologically confirmed cases and 717 randomly selected population-based controls were included in this study. An in-person interview was conducted using a standardized and structured questionnaire to collect information on menstrual and reproductive factors and potential confounding factors. Compared with nulliparous women, women who had four or more pregnancies during their lifetime were found to have a significantly reduced risk of non-Hodgkin's lymphoma (odds ratio (OR) = 0.6, 95% confidence interval (CI): 0.4, 0.9). Risk appeared to decrease with increasing number of pregnancies (p(trend) = 0.03). The authors also observed an increased risk of non-Hodgkin's lymphoma overall (OR = 1.5, 95% CI: 1.0, 2.2) and of diffuse non-Hodgkin's lymphoma (OR = 1.7, 95% CI: 1.1, 2.7) for women who started their first menstrual period at age 15 or more years compared with those who started their first menstrual period before age 12 years. These findings support a reduced risk of non-Hodgkin's lymphoma associated with multiple pregnancies and an increased risk of non-Hodgkin's lymphoma associated with later age at menarche.