Oral retinoids are effective in the treatment of psoriasis, but their use is limited by concerns for teratogenic potential and systemic side effects. Tazarotene is a novel acetylenic retinoid undergoing clinical trials for the topical treatment of mild-to-moderate plaque psoriasis. The safety and tolerability of tazarotene 0.1% and 0.05% gels were examined in a series of preclinical and clinical trials. In preclinical studies topically applied tazarotene gel was nonmutagenic, noncarcinogenic, and nonteratogenic. Tazarotene gel was not sensitizing, phototoxic, or photosensitizing in a series of studies in human volunteers. Treatment-related systemic adverse effects were not observed in clinical trials involving approximately 2000 patients treated with tazarotene 0.1% or 0.05% gel for periods of up to 1 year. Adverse effects appear limited to manageable, mainly mild-to-moderate local skin irritation.