Human sera contained heat stable (56 C) nonspecific inhibitor for influenza A and B hemagglutinin but not for influenza C. This inhibitor appeared to be of the alpha type and was destroyed by treating with filtrate from cultures of Vibrio cholerae which were rich in Burnet's receptor destroying enzyme. This procedure did not have a demonstrable effect on antibody.The PR8, FM1 and Lee strains of virus used in the Standard Hemagglutination-Inhibition Reference Test in Influenza Studies were highly sensitive to the alpha inhibitor. The inhibitor content for these and other strains often exceeded the amount of antibody. The reliability and sensitivity of the hemagglutination-inhibition technique for demonstrating antibody increase in paired serum specimens from cases of influenza and from vaccinated persons using the PR8, FM1, Lee and IB1 viruses was markedly improved by treating to remove inhibitor. This resulted primarily from the marked reduction in titer of the first serum specimen. The sensitivity of the test also depended on test virus; thus, the type A prime strains FM1 (1947) and FW-1-50 (1950) were superior to the 1934 PR8 agent for detecting infection with the A prime viruses of contemporary prevalence. The FW-1-50 virus was especially useful for diagnosis since it was essentially unaffected by the alpha inhibitor in human serum and the need for treatment with cholera filtrate was obviated.The importance of removing non-specific inhibitor from sera tested to determine the basic antibody levels in the human population for the various influenza strains was discussed.
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