This abstract demonstrates that non-specific immunoglobulin interactions, of the F(ab')2 region and Fc piece of human IgG may lead to false-positive results in patients being monitored for naturally occurring (pre-existing) or induced human anti-mouse monoclonal Ig antibodies (HAMA). Patient sera tested before administration of murine monoclonal antibodies for immunoscintography or immunotherapy showed 'positive' results when screened by specific ELISA for the presence of pre-existing antibodies to murine immunoglobulin. However, only serum from a patient which had previously received murine monoclonal antibody for immunotherapy, was it possible to show specificity by competitive inhibition. Thus, the use of competitive inhibition by specific antigen (mouse Ig isotype/subtype), sera positive for HAMA or pre-existing HAMA can be distinguished from false-positive reactions.