Anti-tyrosinase antibodies were measured by enzyme-linked immunosorbent assay in sera of patients with malignant melanoma with either metastatic disease or no evidence of disease, in patients with melanoma and associated hypopigmentation (MAH), in patients with vitiligo and in healthy volunteers. The mean relative absorbance (Arel) was calculated by dividing the absorbance of each sample by the mean value for the control group. Using this method, the Arel of the control group was 1.000(SE 0.083). Arel of patients with metastatic disease (1.516; SE 0.225) was significantly higher (P = 0.03) than the value for the controls, but insignificantly higher than that for patients with no evidence of disease (1.216; SE 0.148). Patients with no evidence of disease, in whom the primary lesion originated in the lower limb, had a significantly higher (P = 0.01) Arel than the healthy volunteers. Patients with metastatic disease showed higher Arel if their primary lesions were confined to the area of the head and neck or to the lower limb. Patients with vitiligo had higher Arel values for their anti-tyrosinase antibody than any of the other groups. However, those with melanoma and MAH (vitiligo-like) had the same Arel of anti-tyrosinase antibodies as the controls or the patients with metastatic melanoma. This observation reflected the possible absorption of anti-tyrosinase antibodies to melanoma antigens, and pointed to the participation of anti-tyrosinase antibodies in the destruction of normal melanocytes in patients with melanoma, as part of the immune reaction towards this disease.