A population of 549 HIV-positive intravenous drug users, 140 of whom were women, recruited between June 1985 and June 1991, were studied to determine the usefulness of minor clinical signs and biological parameters in predicting progression to AIDS at different CD4+ levels. Ninety-eight subjects developed AIDS during a median follow-up of 4 years. Oral thrush was predictive of progression to AIDS independently of the CD4+ level at enrollment; seborrheic dermatitis was predictive of disease progression only in those with CD4+ under 500 cells/mm3. Regarding the predictive value of the biologic parameters examined, similar IgA levels among HIV-seropositive intravenous drug users with CD4+ > 500 cells/mm3 and HIV-negative intravenous drug users were observed, while higher median levels were found among HIV-positive participants with CD4+ level under 500 cells/mm3. Among intravenous drug users with CD4+ < 500 cells/mm3, a level of IgA higher than 200 mg/dl at enrollment was predictive of faster progression to AIDS. Among participants with CD4+ [corrected] over 500 cells/mm3, an IgA level above 400 mg/dl was still predictive of faster progression, but the sensitivity tended to be low. These findings suggest that an elevated level of IgA and presence of oral thrush may be important early markers of disease progression in HIV-infected intravenous drug users. Seborrheic dermatitis is also predictive, but only in later stages.