Application of retinoic acid (vitamin A acid) to animal and human skin has been reported to produce cutaneous, proliferative lesions which microscopically and histochemically resemble those of psoriasis. In the present studies, the daily application of a 0.1 % solution of retinoic acid to the dorsal ear surface of guinea pigs produced a progressive psoriasiform scaling which was apparent grossly and which could be quantitated. Triamcinolone acetonide, hydrocortisone and methotrexate, all known to be useful clinically in the treatment of psoriasis, were examined for their ability to antagonize the development of retinoic-acid-induced scaling. Systemic activity was observed with all three agents; topical activity was obtained with triamcinolone acetonide but not with methotrexate or several of its analogs. On the basis of activity profiles obtained with standard anti-psoriatic compounds, it is suggested that retinoic acid lesions may have utility in identifying the anti-psoriatic potential of new compounds.