Infection with human immunodeficiency virus type 1 (HIV-1) induces vigorous and persistent cytotoxic CD8+ T cell responses. CTL clones were derived from peripheral blood or cerebrospinal fluid of three HIV-1 patients, with depressed CD4+ T cell counts. When stimulated with HLA-compatible target cells (B-LCL) presensitized with cognate HIV-1 peptides, all clones produced GM-CSF, TNF-alpha, and IFN-gamma and most produced low amounts of IL2, IL3, and IL4. After nonspecific stimulation with a phorbol ester and calcium ionophore, the clones secreted cytokines at levels similar to those from CD4+ lines from an HIV-1 infected donor. The ability of supernatants from the stimulated CTL clones to support the formation of granulocyte-macrophage colonies in normal bone marrow suggests that the GM-CSF was biologically active. Release of cytokines by activated CTL may influence the immunopathogenesis of HIV disease.