Antibodies to pertussis toxin were measured by a neutralization test (Chinese hamster ovary cell assay) in paired serum samples from 122 patients with whooping cough. The results were compared with previously published titers of IgG, IgM, and IgA measured by ELISA. Significant (fourfold or more) increases in neutralizing antibodies developed in 69 patients. Sixty-eight of them also had significant increases in at least one antibody class as measured by ELISA. Seventeen patients had significant increases in at least one antibody class without increases in neutralizing antibodies. All 163 serum samples with neutralizing antibodies also had detectable IgG, whereas 14 samples with IgG and 18 with IgM were negative by neutralization test. Thus, toxin-neutralizing serum antibodies develop in most patients with pertussis. Our ELISA, however, was more sensitive in detecting low levels of antibodies and in demonstrating significant increases between acute- and convalescent-phase serum samples.