BACKGROUND: A number of medications have been reported to induce psoriasis. We report two cases of fluoxetine-related psoriasis and discuss similarities between lithium-, trazodone hydrochloride-, and fluxetine-induced psoriasis. OBSERVATIONS: Two women being treated for depression with fluoxetine developed psoriasis after 6 and 12 months' exposure. This time frame is clinically similar to that observed with lithium-induced psoriasis. CONCLUSIONS: The occurrence of lithium- and fluoxetine-induced psoriasis may not be random. Both drugs modulate serotonergic function, a factor that may contribute to the pathophysiology of psoriasis. If a patient on acute or long-term fluoxetine therapy develops psoriasis, the drug should be considered as a possible etiologic agent.