Plasma membrane damage induced in various cell targets by hematoporphyrin (HPD) photodynamic therapy (PDT) could modify cancer cell adhesiveness, an important parameter in cancer metastasis. We investigated the effect of HPD or HPD incubation followed by argon laser light on the adhesiveness of progressive (PROb) or regressive (REGb) cancer cells of the same colonic origin but with a different in vivo metastatic potential. Adhesiveness was studied on plastic or endothelial cell monolayers (ECM). In the absence of treatment, both PROb and REGb cells adhered better on plastic than on ECM. HPD alone or HPD-PDT induced toxicity proportional to the HPD dose. HPD-PDT increased the adhesiveness rate of both cell lines on plastic and decreased it on ECM. HPD-PDT of ECM increased adhesiveness, but only at HPD doses causing at least 50% cell death. With HPD treatment alone or HPD-PDT of culture media, there was no significant decrease in cell adhesiveness to ECM. We also studied the effect of HPD or HPD incubation followed by argon laser light on the metastatic potential of cancer cells, which was decreased for PROb with HPD alone or HPD-PDT. Decreased adhesiveness of colonic cancer cells to ECM after HPD-PDT was thus correlated with decreased metastatic potential. REGb cells did not acquire a progressive phenotype either in vitro or in vivo after HPD-PDT.