To investigate whether the human immunodeficiency virus (HIV) infection or the abuse of narcotic drugs or other viral infections may be responsible for immunologic abnormalities in parenteral drug abusers, sera from 168 consecutive individual patients were collected from 1985 to 1986. The sera were tested for antibody to HIV (anti-HIV), and the clinical, immunologic, and serologic characteristics of 83 seropositive and 53 seronegative parenteral drug abusers were compared. The presence of anti-HIV was significantly associated with a decreased number of T helper lymphocytes (P less than .001), a reduced T helper/suppressor ratio (P less than .001). Of the 83 seropositive patients, 63 (76%) had generalized lymphadenopathy and 16 (18%) had AIDS-related complex. No patient had AIDS. Parenteral drug abusers with AIDS-related complex had significant reductions in the number of T helper cells (P less than .01) and the T helper/suppressor ratio (P less than .01) compared with patients with lymphadenopathy syndrome (LAS), suggesting that parenteral drug abusers with HIV infection develop a progressive immunodeficiency. IgG antibody to cytomegalovirus was found in 75% of anti-HIV-positive and 45% of anti-HIV-negative parenteral drug abusers (P less than .01), but significant associations between anti-HIV and markers for other viruses were not found. Our data confirm that HIV infection is the major cause of low T helper cells and reversed T helper/suppressor ratio in parenteral drug abusers.(ABSTRACT TRUNCATED AT 250 WORDS)