Depigmentary effects of 4-tertiary butyl catechol (TBC) on UV-stimulated melanocytes on the flanks and naturally active melanocytes of ears were compared in Uscd strain hairless mice. UVB irradiation, twice a week for 1 or 2 mo, induced brown-black pigmentation on the flanks. A 1 M TBC application twice a week for 1 mo not only prevented the UV-stimulated pigmentation, but also promoted fading of the post-UV tanning. Dopa-stained split epidermal sheets showed a decrease in the number of melanocytes to less than one-half during the first month of TBC treatment. Melanocytes were often enlarged or lost their dendrites, and both premelanosomes and melanosomes showed ultrastructural changes. However, TBC application on the ears for 1 mo showed neither color change nor a decrease in the number of melanocytes. There were ultrastructural changes in melanocytes but the degree of abnormality was much less than those seen in UV-stimulated melanocytes. Continuation of TBC application for 2 mo with the UV irradiation on the flanks or the nonirradiated ears caused an increase in the number of melanocytes. These results suggest that the initial effect of TBC may be primarily cytotoxicity to melanocytes, and may correlate with their cellular functions. The stimulatory effects of TBC on melanocytes seen during the longer period of time requires further investigation.