Recombinant human interferon beta (rIFN-beta) reduces replication of HIV in cultured peripheral mononuclear cells. The effect is most pronounced when high levels of the drug are employed. Maintenance of the rIFN-beta in culture is required since removal of the agent generally leads to a return of virus production by the infected cells. Moreover, at low concentrations of the drug, a breakthrough in HIV replication is observed. High concentrations of the rIFN-beta (greater than 100 units/ml) were cytotoxic for transformed T cells. This latter observations suggests that rIFN-beta might be useful in human T-cell malignancies. Beta interferon therefore might be useful for the treatment of HIV infection, particularly since side effects of the drug are limited in treated individuals.