Prostaglandin (PG) E2 gel and gel alone were topically applied to the psoriatic lesions of ten patients. After a few days, all PG E2-treated lesions improved, but a complete clearing, could not be achieved. Together with results from the literature, our findings strengthen the hypothesis that cyclo-oxygenase activity is endogeneously inhibited in the psoriatic plaque, thus preventing formation of PG E2 and other metabolites. Replenishing of one of these substances (E2) improved the treated lesion, thus demonstrating that a decrease of PG E2 level might be one important factor in the pathogenesis of the psoriatic lesion.