The role of complement in infections by dermatophytes is unknown. Therefore we evaluated the ability of the dermatophyte Trichophyton rubrum to activate complement in vitro. Aliquots of human plasma that had been incubated with T. rubrum were examined for evidence of complement activation. Following incubation, the total hemolytic complement activity of plasma fell 76%. Further, each T. rubrum incubation led to obvious C3 conversion and generation of polymorphonuclear leukocyte (PMN) aggregating activity. Plasma that had complement activity depleted by heat (56°C x 30 min) or 10 mM EDTA failed to develop C3 conversion or PMN aggregating activity. Complement activation was not affected when the classical complement pathway was selectively blocked by MgEGTA. These studies indicate that T. rubrum can activate the complement system by the alternative pathway. The consequent generation of anaphylatoxins, chemotaxins, and opsonins might be important both in host defense against dermatophytic infections and in the inflammatory reactions mediated by them.