The simian acquired immunodeficiency syndrome (SAIDS) in macaques at the Washington Regional Primate Research Center is associated with a type D retrovirus known as SAIDS-D/WA. We tested the ability of 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxycytidine (ddC), and 2',3'-dideoxyadenosine (ddA) to inhibit the in vitro cytopathic effect (syncytium formation) and infectivity of the SAIDS-D/WA virus. Raji cell cultures were infected with virus and treated with various concentrations of AZT, ddC, and ddA. The ability of these drugs to inhibit replication of the SAIDS-D/WA virus in Raji cells was monitored by syncytium formation, expression of viral antigen, and reverse transcriptase assay. At concentrations of 4, 40, and 400 microM, AZT completely blocked the viral infectivity and inhibited the cytopathic effect of SAIDS-D/WA. Likewise, ddC was inhibitory at concentrations of 5 and 50 microM and ddA was inhibitory at 100 and 200 microM. AZT, ddC, and ddA became cytostatic to Raji cells with increasing drug concentrations. AZT also partially inhibited SAIDS-D/WA replication in previously infected Raji cell cultures, and viral inhibition increased in response to the concentration of AZT. These data indicate that AZT, ddC, and ddA are effective antiretroviral agents that merit further evaluation, including clinical trials, in animal models with AIDS-like diseases.