Flow cytometry (FCM) was used to investigate the effect of mitomycin C (MC) on the cellular uptake of Photofrin II (PII) in a cultured human colon adenocarcinoma cell line (WiDr). The surface area of the cells increased as they passed through the cell cycle from G0/G1 to G2/M phase. MC retarded the cells in G2/M phase and enhanced the surface area of the cells. A 1.3-2.3-fold increase in the cell surface area and a 1.3-2.7-fold increase in the cellular uptake of PII in the tumor cells was observed after 2 h-8 h incubation with MC. Within each sample, an almost linear relationship between the intensity of PII fluorescence in the cells and the surface area of the cells was found. However, for the cells incubated with MC the surface area was not the only determinant of PII uptake. Effects of MC on the cell cycle, the cell surface area and the permeability of the cell membrane are suggested as possible reasons for the increase of cellular uptake of PII in the tumor cells.