Pertussis toxin (PT) is an important virulence factor of Bordetella pertussis, the causative agent of pertussis. Bordetella parapertussis also causes a pertussislike disease in humans. Most strains of B. parapertussisexamined contain regions highly homologous to the ptx region of B. pertussis, however this region is transcriptionally silent due to numerous mutations in the ptx promoter region. Three of 32 children with B. parapertussis disease exhibited a modest increase in antibody titer to PT during the course of their disease. We examined one of these 3 clinical isolates (BPP10978) for production of PT. Under the conditions of growth that we examined, this strain did not make PT. In order to determine whether this strain could produce a functional PT if the promoter were active under certain, as yet undefined conditions, we replaced the B. parapertussis promoter and a portion of the PT S1 subunit cistron of BPP10978 with the homologous region from B. pertussis. The resulting exconjugate was found to produce a small amount of labile, active toxin. These results demonstrate that clinical isolates of B. parapertussis contain genes which encode biologically active PT and suggest that if the ptx promoter of these strains were active under certain conditions, the strains would be capable of producing low levels of active PT.