Oxygen-centred free radicals play an important role in the pathogenesis of acute and chronic UV-induced skin damage as well as in skin aging. In this double-blind randomized study the efficacy of topically applied melatonin (N-acetyl-5-methoxytryptamine), a potent free radical scavenger, in the suppression of UV-induced erythema was assessed. A group of 20 healthy volunteers were irradiated with 0.099 J/cm2 UVB on four 5-cm2 areas on the lower back and topically treated with various concentrations of melatonin (0.05, 0.1, 0.5%) in a nanocolloid gel as carrier or with carrier alone. The UV-induced erythema was examined 8 and 24 h after irradiation by visual scoring and chromametry. A distinct dose response relationship was observed between the topical dose of melatonin and the degree of UV-induced erythema. Significant differences (P < 0.05) were found in redness (chromameter a-value and visual scoring) 8 h after irradiation between the areas treated with melatonin at 0.5% and those treated with melatonin at 0.05% or with the carrier. These results might open a new approach in the prevention and control of free radical-influenced skin diseases.