We have investigated the malignant cell selective phototoxicity of some triarylmethane dyes including Victoria Blue BO (VB-BO), Victoria Blue R (VB-R), and Malachite Green (MG). Phototoxicity was studied in human squamous (FaDu) and colon (CX-1) carcinoma, and in human and murine melanoma (NEL, B-16) cell lines, as well as in non-malignant monkey kidney cells (CV-1). Cultured cells were exposed to varying concentrations of the dyes for 60 min, washed with PBS, irradiated after an efflux time of 90 min in culture media, and placed in a colony forming assay. VB-BO was the most effective photosensitizer, giving 90% killing of malignant cells such as B-16 when treated with 5x10-8 M dye and 13 J/cm2 light. CV-1 cells were unaffected under these conditions. VB-R was about 10 fold less effective, while MG had minimal phototoxicity in this assay. VB-BO was studied in vivo, using subcutaneous FaDu tumors in nude mice. At a dose of 3 mg/kg followed 4 hrs later by dye laser irradiation under conditions which did not produce hyperthermia, there was an 80% complete remission rate without significant phototoxicity to overlying or adjacent normal skin. The triarylmethanes are a novel class of photosensitizers which may have promise in vitro and in vivo.