Sera from patients with lepromatous leprosy show a high incidence of a chemotactic inhibitor. This inhibitor acts directly on leukotactic factors (bacterial chemotactic factor, C3 [the 3rd complement component] fragment and C5 fragment) to render the factors irreversibly inactive. Functinally, the inhibitor acts as a chemotactic factor inactivator. While normal serum shows no inhibitory activity under the conditions employed, inhibitory activity causing > 30% reduction of the bacterial chemotactic factor was found in the sera from 14 to 19 patients with lepromatous leprosy. Although exceptions were noted, a correlation was found between the presence of the inhibitor and depressed skin reactivity to a series of antigens (lepromin, trichopytin, Candida, PPD [purified protein derivative] and mumps antigen) used for elicitation of delayed-type hypersensitivity reactions. The presence in leprosy sera of this inhibitor may be responsible, at least in part, for some of the defects of cellular inflammatory responses in patients with lepromatous leprosy.