Malignant lymphomas are a group of diseases of uncertain etiology. Both environmental factors and genetic susceptibility have been reported as risk factors. We have conducted a population-based case-control study in Italy: all newly diagnosed cases of malignant lymphoma, in males and females ages 20 to 74 years in the 1991 to 1993 period, were identified; the control group was comprised of a random sample of the general population resident in each of the areas under study, stratified by sex and 5-year age groups. Overall, 1,428 non -Hodgkin lymphoma (NHL) cases and 1,530 controls were interviewed. Experts from each geographic area examined questionnaire data and assigned a level of probability and intensity of exposure to a range of chemical groups and individual chemicals. For those in the medium/high level of exposure, there was an increased risk of NHL for exposure to benzene, xylene, and toluene. We have examined the hypothesis that the effect of solvents is related to their immunotoxicity by analyzing the interaction with a previous history of autoimmune disease. We have found an apparent, though not statistically significant, increased risk of NHL in those with both exposure to benzene and a history of autoimmune disease (odds ratio, 16.3; 95% confidence interval, 0.8-321). In addition, an odds ratio of 29.8 (95% confidence interval, 1.4-650.2, based on nine exposed cases) was associated with high-level exposure to benzene in those with a positive family history of malignant hematologic neoplasms. Both hypotheses (i.e., the interaction with autoimmune diseases and with familial predisposition) indirectly suggest that an immunologic mechanism could be involved in lymphomagenesis from solvents. (Cancer Epidemiol Biomarkers Prev 2007;16(3):381 -4)