Synthetic retinoids that have distinct therapeutic activity on psoriatic plaques act at least in part through the metabolic pathways of natural retinoids. The metabolism of retinol, retinal, and retinoic acid in human epidermis in general and psoriatic plaques in particular has not been previously analyzed. This appears to be an important issue, because enzymatic formation of retinoic acid from retinol within target cells is thought to be the source of biologically active retinoic acid therein and might be subjected to regulation. We found chat the enzymatic system that transforms (3H)retinol into (3H)retinoic acid is detectable in psoriatic plaques (0.33 +/- 0.07 pmol/h/mg protein) but only in trace amounts in normal epidermis. The activity due to alcohol deshydrogenase seems not to be involved in this process. (3H)retinal was found to be either reduced into retinol or oxidized into retinoic acid, depending on the ratio of NAD to NADH (the oxidized arid reduced nicotinamide-adenine dinucleotide, respectively); the former reaction was higher in psoriatic plaques than in normal epidermis.