Cellular retinoid binding proteins are thought to be involved in the molecular action of retinoids, a family of compounds successfully used in the treatment of psoriasis. Therefore, both cellular retinol (CRBP)- and retinoic acid (CRABP)-binding proteins were analyzed in psoriatic skin. Three facts emerged from our study: both CRABP and CRBP are detectable in the skin of psoriatic patients; qualitatively, they both appear similar to the corresponding proteins of normal human skin, in terms of their elution profile and apparent Kd; and quantitatively, only CRABP was found to be 3 times higher in psoriatic plaques as compared to either nonlesional skin of psoriatic patients or the skin of normal subjects. Since psoriatic plaques are particularly responsive to systemic retinoids, specifically to retinoic acid analogues, our results suggest for the first time a link between the levels of CRABP and the responsiveness of a nonneoplastic hyperproliferative tissue to systemic administration of retinoids in the human.