The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were investigated using MTT assay against two human retinoblastoma cell lines, Y79 and WERI-Rb-1. Y79 and WERI-Rb-1 were totally resistant to doses up to 5.0 micrograms/ml of verapamil. Cyclosporin A inhibited the survival of Y79 and WERI-Rb-1 dose-dependently, however, the maximum inhibition at the highest concentration tested (5.0 micrograms/ml) was less than 50% (% survival at 5.0 micrograms/ml of cyclosporin A: 65.6% and 66.9% in Y79 and WERI-Rb-1, respectively). Combination of cyclosporin A and verapamil did not further inhibit the survival of Y79 and WERI-Rb-1 compared with cyclosporin A alone. Adramycin inhibited the survival of Y79 and WERI-Rb-1 dose-dependently. The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were evaluated in terms of sensitizing index (SI: the ratio of IC50 to adriamycin alone to IC50 to adriamycin in the presence of cyclosporin A and/or verapamil). Cyclosporin A significantly enhanced SI and the addition of verapamil enhanced SI further: SI values at 5.0 micrograms/ml of cyclosporin A, 5.0 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of verapamil, 5.0 micrograms/ml of cyclosporin A plus 3.0 micrograms/ml of verapamil were 2.0, 2.6 and 2.8 in Y79 and 2.6, 5.8 and 9.7 in WERI-Rb-1, respectively. These results suggest that cyclosporin A and verapamil are promising chemosensitizers to adriamycin in the treatment of retinoblastoma.