SummaryPreviousin vivostudies have shown that 4‐S‐cysteaminylphenol (4‐S‐CAP) and N‐acetly‐4‐S‐ cysteaminylphenol (N‐Ac‐4‐S‐CAP) have antimelanoma effects and that N‐Ac‐4‐S‐CAP produced a 98% depigmentation of hair follicles of black mice. This study investigated the process of selective melanocytotoxicity by N‐Ac‐4‐S‐CAP through light and electron microscopy studies of hair follicles obtained from newborn black mice treated with N‐Ac‐4‐S‐CAP. Visible changes in follicular melanocytes were found 4h after intraperitoneal (i.p.) adminstration. Clumps of melanin granules and areas of melanocytic nuclear condensation were seen in the hair follicles. On electron microscopy there was progressive destruction of melanoctyes with swelling of membranous organelles, nuclear condensation, and vacuolation of the cytoplasm, culminating in completely necrotic cells. None of thes changes were demonstrated in the surrounding keratinocytes. N‐Ac‐4‐S‐CAP appears to have specific, cytotoxic effects on melanocytes actively producing eumelanin. The drug may not affect precursor or dormant melanocytes whic retai