Chalcogenapyrylium (CP) dyes which are specifically activated by red and near infrared light (600-900 nm) were examined as potential photosensitizers for photochemotherapy of malignant gliomas. Eleven CP dyes of varying chemical structure and redox potential were evaluated for selective toxicity against glioma and normal skin fibroblast cell cultures both before and after light activation. Eight of eleven CP dyes exhibited differential toxicity to tumor over fibroblast cells at dye concentrations of 1.0 microM. Dose dependent toxicity was seen both in the dark and after laser light activation. The toxicity of two of the CP dyes was significantly enhanced by photoactivation with 800 nm light. The CP dyes that absorb light maximally between 775 and 850 nm, in the range of excellent light penetration through brain, appear to be promising candidates as photosensitizers for treating malignant brain tumors.