Recombinant human interferon alfa-A (rIFN alpha A) had a dose-related suppressive effect on human T lymphotropic virus type III (HTLV-III) replication in vitro in normal peripheral-blood mononuclear cells (PBMC). Both single-dose and multiple-dose regimens were inhibitory. Such inhibitory concentrations (4-1024 units/ml) were not toxic to PBMC in culture, and were within the ranges achievable in blood after injection. These studies suggest that clinical trials of rIFN alpha A in early HTLV-III infection are warranted.