Because of growing evidence that there are differences in the natural history of HIV infection in intravenous drug users (IVDU) and homosexual men, the clinicopathological features and response to treatment of AIDS-related non-Hodgkin's lymphomas (NHL) were analyzed in 150 cases (96 IVDU and 31 homosexual men) by the Italian Cooperative Group on AIDS-related tumors. Twenty-three patients fell within other risk groups. The median age was 26 years for the IVDU and 38 for the homosexual men. Forty percent of patients in both of the risk groups manifested full-blown AIDS prior to development of the lymphoma. In both groups, most of the NHL were of high or intermediate type (IVDU 96%, homosexual men 86%). In high-grade NHL, Burkitt's type lymphoma was present in 40% of the homosexual men and in 29% of the IVDU (a non-significant difference), while an immunoblastic lymphoma was diagnosed in 46% of IVDU and 27% of homosexual men (non-significant). No oral localizations were observed, and one homosexual presented with a rectal lymphoma. Almost half of the patients (47%) received no antineoplastic treatment because of rapid disease progression or of diagnosis only at post-mortem. Intensive combination regimens administered in one-third of both IVDU and homosexual men (compared to CHOP or CHOP-like combinations) provided more CR (3/13 vs 3/24 in IVDU and 2/3 vs 1/7 in homosexuals), although the overall survivals with both the intensive and less intensive chemotherapy protocols remained similar. Overall, the median survival was 3.7 months for IVDU and 3.6 months for homosexual men. The most reliable predictors for survival were opportunistic infections at onset in IVDU.(ABSTRACT TRUNCATED AT 250 WORDS)