The hormone melatonin is produced in the pineal gland and secreted into the blood in a circadian rhythm. Due to its antiox-idative and immunomodulatory effects it might play a role as a topical drug in dermatology. In this study we investigated the penetration kinetics of melatonin applied to the skin of 6 healthy volunteers aged 26-34 years (M/F = 2/4). First the individual physiologic daytime melatonin serum levels were determined by radioimmunoassay. Then 3 of the participants were treated once topically on their scalp with 20 mg melatonin dissolved in 70% ethanol, while the other 3 individuals received 100 mg. The application was performed at 9.00 a.m., and blood samples were collected repeatedly for a total of 8 h. Physiologic daytime melatonin levels in the 6 individuals were 16.8 ± 10.0 pg/ml. The 3 individuals treated with 20 mg melatonin displayed peak serum levels of 762, 918 and 3,440 pg/ml, respectively, those treated with 100 mg melatonin showed peak levels of 1,136, 3,360 and 4,230 pg/ml lasting throughout the entire observation period of 8 h. These findings indicate that melatonin might accumulate in the stratum corneum with prolonged release into the blood system from this depot