Vitiligo is a skin disease with lack of destruction of melanocytes. Factors of humoral immune system such as antimelanocyte antibodies, rheumatoid factors (especially IgM-RF), level of C3, C4 and anti-nuclear antibodies had been studied in the pathogenesis of vitiligo. In this study, sera of 55 patients with vitiligo and 60 normal subjects were examined for detection of antimelanocyte antibodies, anti-nuclear antibodies (ANA) by indirect immunofluorscent test, rheumatoid factor (IgM-RF) by latex and ELlSA methods and C3, C4 using single radial immunodiffusion (SRID) test. Four patients (7.3%) and a normal subject were ANA positive (p>0.05); 14 patients (25.5%) had decreased C3 and C4 (p<0.05) and all sera had normal levels of C3 and C4. In 6 patients (10.8%) and none of normal sera, rheumatoid factor were detected by ELlSA (p=0.005). Antimelanocyte antibodies were detected in 17 (30.9%) patients (p<0.001) and all normal sera were negative for antimelanocyte antibodies. Therefore, immune systems play an important role in vitiligo as an autoimmune disease.