Both interferon gamma (IFN-gamma) produced by T helper 1 (T(H)1) lymphocytes and interleukin-4 (IL-4) produced by T(H)2 lymphocytes were reduced in either bulk circulating mononuclear cells or mitogen-induced CD4(+) T cell clones from the peripheral blood of individuals infected with human immunodeficiency virus (HIV). There was a preferential reduction in clones producing IL-4 and IL-5 in the advanced phases of infection. However, enhanced proportions of CD4(+) T cell clones producing both T(H)1-type and T(H)2-type cytokines (T(H)0 clones) were generated from either skin-infiltrating T cells that had been activated in vivo or peripheral blood T cells stimulated by antigen in vitro when cells were isolated from HIV-infected individuals. All T(H)2 and most T(H)0 clones supported viral replication, although viral replication was not detected in any of the T(H)1 clones infected in vitro with HIV. These results suggest that HIV (i) does not induce a definite T(H)1 to T(H)2 switch, but can favor a shift to the T(H)0 phenotype in response to recall antigens, and (ii) preferentially replicates in CD4(+) T cells producing T(H)2-type cytokines (T(H)2 and T(H)0).