Photodynamic treatment (PDT) employs a photosensitizer and the light-induced formation of reactive oxygen species--antagonized by cellular antioxidant systems--for the removal of harmful cells. This study addresses the effect of altered carbohydrate metabolism on the cellular antioxidant glutathione system, and the subsequent responses to PDT. It is shown that glucose-deprivation of 18 h prior to PDT causes a reduced level of intracellular glutathione and an increased cytotoxicity of PDT. These effects can be mimicked by inhibitors of glutathione synthesis (buthionine-sulfoximine) or its regeneration (1,3-bis-(2-chlorethyl)-1-nitrosourea). Inhibited glutathione metabolism shifts the apoptotic window to lower fluences, while glucose deprivation abolishes apoptosis as a result of ATP deficiency. Our results prove evidence for manipulation of the outcome of PDT through internal metabolic pathways.