The human serologic response to several envelope-associated proteins and adenylate cyclase toxin of Bordetella pertussis was examined using immunoblot techniques. Antigens recognized by sera from individuals with culture-confirmed pertussis and by sera from infants immunized with three doses of conventional whole-cell pertussis vaccine included a 63,000-Da protein that was shown to be antigenically related to a mycobacterial heat-shock protein. A 29,000-Da protein reacted with sera from convalescent individuals, whereas a 91,000-Da protein reacted with sera from vaccinated individuals. Antibodies to adenylate cyclase toxin were common in sera from individuals diagnosed with pertussis. B. pertussis lipooligosaccharide was also recognized by antibodies in some of these sera. These data suggest that some of these antigens may play a role in immunity to pertussis.