Two patients with severe generalized psoriasis and psoriatic arthritis whose conditions had failed to respond to oral therapy with traditional remedies, including etretinate (both patients) and its combination with psoralen and UV-A (PUVA) (one patient) were successfully treated with minimal oral dosages of the arotinoid RO 13-6298 (0.05 to 0.1 mg/day). Side effects of this new synthetic retinoid included dryness of the lips and nasal mucosa, some palmarplantar desquamation, gross thinning of the skin, itching, and transient hair loss. Laboratory investigations disclosed no abnormalities attributable to the drug. The new arotinoid, RO 13-6298, seems to be a highly potent retinoid in its antipsoriatic effects. It represents the third generation of synthetic retinoids that may be effective in extremely low doses.