SDS-PAGE analysis of the soluble proteins of the yeast Saccharomyces cerevisiae revealed a single predominant moiety of apparent size 200 kDa which was strongly periodic acid Schiff-positive. In immunoblotting experiments, human sera containing anti-S. cerevisiae antibodies were reactive only with this glycoprotein (gp200); this was demonstrated using sera containing IgG and IgA isotype-specific anti-S. cerevisiae antibodies. The antigenicity of gp200 was substantially reduced by periodate treatment. These results show that gp200 is a major glycoprotein antigen of S. cerevisiae which is immunogenic in man.