Differences in skin pigmentation may significantly affect light penetration during photodynamic therapy. This study evaluated the effect of skin pigmentation on dermatotoxic reaction to photodynamic therapy utilizing the photosensitizer dihematoporphyrin ether. Black and white guinea pigs were given 10 mg/kg of dihematoporphyrin ether, depilated, and treated 48 hours after injection with 30 mW/cm2 of 514-nm light. Eschar formation was observed on white skin at an average light dose of 26 J/cm2, whereas black skin showed similar changes at 58 J/cm2. Microscopically, superficial necrosis corresponded to the gross changes noted. Our results agree with data describing the difficulty of treating pigmented lesions such as malignant melanoma with photodynamic therapy. This further suggests that higher light doses may be required to treat superficial lesions and produce skin photosensitivity in dark-skinned individuals.