The effect of 3'-azido-3'-deoxythymidine (AZT) on in vitro infection of peripheral blood mononuclear cells (PBMCs) isolated from normal adult individuals with human T cell leukaemia/lymphoma virus type I (HTLV-I) was evaluated. Different PBMC samples were exposed to HTLV-I by cocultivation with MT-2 (a chronically infected cell line) in the presence of 20 U/ml of human recombinant interleukin 2 (IL-2) and graded concentrations of AZT. Control and drug-treated cultures, of both infected and uninfected PBMCs, were then grown for several weeks and monitored for virological and immunological parameters. The results showed a concentration-dependent anti-proliferative effect of AZT in both infected and non-infected cultures. Production of both proviral DNA and viral RNA was inhibited not only at the higher concentrations of AZT (8 microM and 32 microM) but also at concentrations as low as 0.1-2 microM. These results were confirmed by PCR and by flow cytometry analysis for the viral core protein p19. Moreover, treatment with AZT resulted in a decreased expression of CD25 in cultures exposed to HTLV-I as well as in non-infected PBMCs. On the other hand, HLA-DR was down-regulated to a greater extent in drug-treated, virus-exposed cultures in comparison with those not infected. No evidence of the antiviral activity of AZT was observed in PBMC cultures already infected by HTLV-I or in MT-2 cells. These findings demonstrate that treatment with AZT, when given at the time of infection with HTLV-I, has a marked protective effect on PBMCs.