HIV-1 infection of human CD4+ lymphocyte cell lines results in cell death. Treatment, but not pretreatment, of infected cells, with a fluoroquinolone antibiotic, DR-3355, protects a significant subfraction of cells from HIV-1-mediated cytolysis. All surviving cells have lost expression of the CD4 antigen, but do (MT-4) or do not (CEM) express viral antigens and produce infective virus. The rescued CEM and MT-4 cells are phenotypically stable and do not require continuous exposure to the drug for survival.