Previous work in 3 subjects infected for 2 weeks indicated that experimental infection with Haemophilus ducreyi recruits CD4 cells to the skin at the pustular stage of disease. In order to describe the kinetics of the host response, 23 subjects were infected at 2 sites with a standardized dose of H. ducreyi. Subjects were biopsied 1 or 4 days after inoculation or when they developed a painful pustular lesion (days 7-14). Papules and pustules contained a predominant T cell infiltrate that consisted of CD45RO and CD4 cells of the alpha beta lineage. Both papules and pustules contained mixed or T helper 1 type cytokine mRNA and interleukin-8 and tumor necrosis factor-alpha mRNA. Although the subjects had no history of chancroid, their immune responses resembled delayed-type hypersensitivity reactions that occurred within 24 h of inoculation and persisted throughout the course of experimental infection.