Net interleukin-1 (IL-1) inhibitor activity is induced by exposure of purified human monocytes-macrophages to respiratory syncytial virus (RSV). Furthermore, IL-1 inhibitor activity was produced by monocytes-macrophages exposed to RSV in the presence of lymphocytes, that is, by unseparated mononuclear leukocytes (MNL). Purified RSV-exposed lymphocytes, as well as the lymphocytes exposed within MNL preparations, produced net IL-1 inhibitor activity. In contrast, net IL-1 activity was produced when purified monocytes-macrophages or unseparated MNL were exposed to influenza virus. The RSV-induced IL-1 inhibitors demonstrated antiproliferative effects on mitogen-stimulated human lymphocytes as well as on the mouse thymocytes used in standard assays. The results raise the possibility that such antiproliferative activity is mediated, at least in part, by monocytes-macrophages. The data also suggest that IL-1 inhibitors produced by MNL after exposure to RSV may contribute along with other factors to the recurrence of RSV infection in immune individuals.