The present study evaluates the impact of the fluence rate of red light irradiation ((lambda) = 650 nm) on photodynamic efficacy in mTHPC-sensitized HT29 and Colo26 spheroids. Photocytotoxicity, computed as product of the cell yield and plating efficiency, increased progressively when the fluence rate was reduced from 90 to 30 mW cm<SUP>-2</SUP> in both types of spheroids. The observed photocytotoxicity was mainly due to an immediate rather than a delayed cell death for HT29 spheroids. An opposite effect was observed for Colo26 spheroids. The plausible explanations could be the difference in penetration of mTHPC into the spheroids as well as their heterogeneous structure.