Topical retinoids are of potential value in the treatment of psoriasis. The aim of the present study was to find out whether topical application of 13-cis-retinoic acid (13-cis-RA) has an antipsoriatic effect. Nine patients participated in the investigation. In each patient, two comparable psoriatic lesions (5 x 5 cm or more) were selected for treatment with either 13-cis-RA in a 0.1% cream base or with the vehicle only (placebo), using a double-blind approach. The investigation was a left-right within-subject comparison. The lesions were recorded for clinical scores 4 weeks before and after the investigation. Punch biopsies were taken from eight patients before and after treatment and examined using immunohistochemical methods to assess epidermal proliferation and keratinization, and to assess inflammation. Thirteen-cis-RA treatment resulted in a mild decrease of scaling and induration. Erythema however increased. No statistically significant difference in biological effects was achieved between 13-cis-RA and placebo treated lesions and no changes in expression of the immunohistochemical markers were seen.