HIV-1 replicative activity and its relation to the clinical and immunological evolution of infection was studied in a group of 150 HIV-1 seropositive Italian i.v. drug abusers over a 1 year period. HIV-1 was isolated from 90 (60%) subjects; two groups of isolates were distinguished, according to replicative activity "in vitro" and ability to induce cytopathic effects in cell cultures, and were termed "rapid-high" and "slow-low" viruses, in agreement with other workers. Rapid-high viruses were recovered more frequently from patients with ARC/AIDS, while slow-low viruses seemed related to the asymptomatic period of infection. The replicative properties of HIV-1 seem to affect strongly the course of disease. In fact, an important CD4 cell decline occurred in asymptomatic subjects with rapid-high virus infection; asymptomatic subjects with negative viral cultures or with slow-low viruses showed no such decline. Asymptomatic subjects with negative viral cultures had no signs of disease during the observation period, while 9% with slow-low virus and 45% with rapid-high virus progressed to AIDS.