The new immunoradiometric assay for CA125 (CA125II assay) uses the monoclonal antibody M11 as an immunoadsorbent. The epitope recognized by M11 is different from the OC125 epitope. Monoclonal antibodies 130-22 and 145-9 recognize an epitope designated as CA130 on the molecule expressing the OC125 epitope. Similarity of M11 epitope to the epitope of anti-CA130 antibodies and dissociation of antigen levels measured by the original CA125 assay and new CA125II assay were examined. Anti-CA130 antibodies partially competed with M11 for the M11 epitope. Among more than 20,000 serum samples we found 12 patients in whom the serum CA125 concentration measured by the CA125II assay was different from that measured by the original assay. In 11 out of 12 patients the CA125 concentration was moderately or extremely high by the original assay but very low by the CA125II assay. Eight of the 11 patients had benign disease, one had no apparent disease and two had cancer. The antigen level determined by CA130 assay was very low in all the 11 patients. In one patient the CA125II assay showed a higher antigen level than the original assay or CA130 assay. The heterogeneity of the epitope expression could cause the dissociation of CA125 levels measured by the different monoclonal antibodies.