Both recombinant alpha A interferon and azidothymidine inhibit the replication of human immunodeficiency virus in peripheral blood mononuclear cells. Combinations of recombinant alpha A interferon and azidothymidine at concentrations that are easily achievable in patients synergistically inhibit human immunodeficiency virus in vitro with minimal toxicity. Combinations of antiretroviral compounds that act by different mechanisms may prove useful in the treatment of acquired immunodeficiency syndrome-related disorders.