To investigate whether drug use affected immunological parameters, we conducted a cross-sectional study of 321 drug users. Absolute numbers of CD4+ lymphocytes and the T-cell reactivity were lower in HIV-positive than in HIV-negative people. The functional capacity of the T-cell system as measured after stimulation with a monoclonal antibody directed against CD3 was found to be strongly associated with the frequency of injecting, while no relationship was found between the frequency of injecting and the total number of lymphocytes or T-cell subsets. HIV-negative and HIV-positive drug users who had injected a mean of three times a day in the preceding 4–6 months had a T-cell reactivity which was 40–50% lower compared with seronegative and with seropositive drug users who had not injected in the preceding months. We conclude that lymphocyte reactivity is depressed by frequent injecting in HIV-negative and HIV-positive drug users.