Pertussigen, a purified protein from Bordetella pertussis, was shown to increase delayed-type hypersensitivity (DTH) to protein antigens in mice. First, it caused an approximately twofold enhancement of the magnitude of 24-h DTH reactions. Second, the peak magnitude of DTH was delayed to 4-7 d after challenge, at which time it was five times more intense than in mice not receiving pertussigen. This reaction was antigen specific, and histologically was characterized by a dense mononuclear infiltrate. Third, pertussigen prolonged DTH so that it was still detectable 3-6 wk after challenge. The effect of pertussigen was seen only in antigen-driven reactions and was time and dose dependent, with 400 ng given 3 d after immunization resulting in the most prolonged reaction. The administration of pertussigen to the recipients of sensitized lymph node cells resulted in DTH that was more intense and prolonged than the reactions in control mice. Administration of pertussigen provides a model of prolonged and enhanced T cell-dependent inflammatory responses.