An old concept to account for autoimmunity is the existence of immunologic cross reactions, or shared determinants between an exogenous agent and self antigen. To study molecular mimicry between the Candida antigen and an autoantigen, sera from clinical specimens were screened, based on seronegativity or positivity for thyroid, ovary and adrenal antibodies. Compared with tissue antibody negative sera and sera from healthy controls, samples from positive tissue antibody subjects exhibited significantly higher levels of Candida IgG (P < 0.001) IgM (P < 0.001) and IgA (P < 0.01) antibodies. While Candida antibodies were elevated in 60% of tissue antibody positive samples, these antibodies were present in only 7.5% of tissue antibody negative subjects and in 10% of healthy controls. Since PAGE electrophoresis showed similar bands mobility in Candida and different tissues, these positive antibodies and rabbit anti Candida antibodies were reacted in immunodiffusion and Western Blot Assay against Candida and tissue antigens, simultaneously. The results of immunodiffusion showed a clear precipitation line against tissue antigens when rabbit anti Candida or human positive Candida serum was used. Similarly, Western Blot Assays with rabbit or human anti Candida serum showed several positive bands with Candida and one or two positive bands with different tissues. The common antigens were located in the regions of 72 and 36 KD. The 72 KD was detected in capsule antigens, placenta, ovary, adrenal, thymus, liver, pancreas, spleen, brain and kidney, but not in sperm or epithelial cell antigen. The 36 KD antigen was positive in placenta, spleen adrenal, pancreas and capsule tissues. Absorbtion of sera containing high levels of Candida antibodies with tissue antigens caused 10-15% reduction in antibody titers. Moreover, treatment of thyroid antibody positive sera with C. Albicans caused a similar reduction in thyroid antibody levels. These reductions in antibody levels are an additional support for cross reactivity between C. Albicans and mammalian tissues. A demonstration of immunological cross reactivity between Candida and human tissues may be associated with the possible pathogenic role of Candida Albicans in the development of autoimmune diseases which warrants further investigation.