BACKGROUND Vitiligo is a common disease of unknown cause. Previous studies have shown abnormalities in natural killer (NK) cell cytotoxicity in patients when NK-sensitive erythroleukemic cell lines were used as target cells. OBJECTIVE The purpose of this study was to use melanocytes directly as target cells to determine NK and lymphokine-activated killer (LAK) cell cytotoxicity in patients with vitiligo and to determine whether NK or LAK cells can be implicated in any destructive mechanism for melanocyte cytotoxicity in vitro in this disease. METHODS Twenty-one patients with vitiligo were compared with a control group by studying NK cell activity (NKCA) and LAK cell activity (LAKCA) on several target cells. These included K562 cells, neonatal melanocytes, and malignant melanoma cells for NKCA and neonatal melanocytes and malignant melanoma cells for LAKCA. Cytotoxicity was measured with the standard chromium 51-release assay. RESULTS No significant differences were found between vitiligo patients and control subjects in NKCA against K562 cells or in NKCA and LAKCA against melanocytes. CONCLUSIONS NK cells and LAK cells are probably not responsible for melanocyte destruction in vitiligo.