The non-antigen specific rapid cytotoxic (CT) death of immature TdT+CD4+CD8+ T cells due to contact with HIV-1 carrier T-cell clones we have found recently is a novel phenomenon. The effects of interferons (IFN) on this CT reaction were studied in vitro. Treatment of the HIV-1 carrier clones, referred to as "effectors," with IFN-alpha but not IFN-gamma, or of the susceptible immature TdT+CD4+CD8+ T cells, referred to as "targets," with IFN-gamma but not IFN-alpha, for 24 hr prior to CT testing was found to reduce the CT reaction. Simultaneously, a down-regulated CD8 expression and an up-regulated antigen expression of both major histocompatibility antigen complex class I (MHC-I) and HIV-1 gp120/gp160 in the IFN-alpha treated effector (gp120+CD8+ HPB-ALL/HIV), and/or simultaneously up-regulated antigen expression of both CD8 and MHC-I in the IFN-gamma treated target (CD4+CD8+ HPB-ALL) were found to be associated with reduced CT reaction. However, altered antigen expression in the IFN-gamma treated effectors or IFN-alpha treated targets did not affect the ultimate degree of CT reaction. This study thus suggests a possible therapeutic efficacy of IFN by reducing the direct elimination of the T-cell precursors in HIV-1 infection.