A case-control study was undertaken to determine whether a prior history of a variety of acquired disorders affecting the immune system was associated with an increased risk of non-Hodgkin's lymphoma. Cases were identified over a 4-year period (1976-1979) at the Johns Hopkins Hospital and individually matched to hospital controls on age, sex, race, and year of diagnosis. For the 109 cases and matched controls who were traced and interviewed, positive associations suggesting an increase in risk were not detected. Instead, there was a suggestion of an inverse relationship. Odds ratios (ORs) were consistently less than 1 for associations between non-Hodgkin's lymphoma and several chronic infectious diseases (OR = 0.65, 95% CI = 0.35, 1.20), chronic inflammatory diseases (OR = 0.88, 95% CI = 0.43, 1.79), autoimmune disorders (OR = 0.80, 95% CI = 0.19, 3.76), and allergic disorders (OR = 0.77, 95% CI = 0.45, 1.32). A statistically significant protective association was found for surgical removal of lymphoid tissue (OR = 0.50, 95% CI = 0.27, 0.91). Adjustment for potentially confounding variables did not change these results. These findings do not support the previously anecdotally reported impression that disorders producing a chronic antigenic stimulus are associated with the development of non-Hodgkin's lymphoma.