The aim of this preliminary report was to measure plasma and skin concentrations of Ro 15–0778 and its phenolic metabolite Ro 14–6113 in hairless rats receiving orally 10 mg/kg of Temarotene once daily during 10 days. Blood (2–3 ml) and skin (200–300 mg) samples were taken at different time points between 0.5 and 240 h after the last dose. We used a highly sensitive HPLC method for simultaneous determination of the two compounds with a quantification limit of 2 ng/ml in plasma and 10 ng/g in total skin (epidermis and dermis). After 10 h, plasma concentrations of Ro 14–6113 were 5–13 times higher than for Ro 15–0778. Ro 14–6113 concentrations in the skin were 4–10 times higher than for Ro 15–0778 within the initial 48 h. The concentrations of both compounds in the skin were higher than conce