Heat-labile toxin (HLT) is a potent toxin produced by Bordetella species. This toxin induces tissue damage and may contribute to damage observed after infection. Only one other toxin, tracheal cytotoxin, is known to be produced by all four species in the genus Bordetella. Since the different species produce similar diseases albeit in different hosts, HLT may play an important role in the pathogenesis of the organisms. We have initiated a program to examine the structure and function of this toxin. We have found that purified HLT induced ischemia in guinea pig skin. When endotoxin contaminates the HLT preparation, the lesions produced are dermonecrotic rather than ischemic in nature. Thus the dermonecrotic lesions that have long been thought to be the hallmark of HLT action are only produced by rather crude preparations of the toxin which contain endotoxin. We have also found that free fatty acids inhibit HLT action. Work is continuing to determine the mechanism of this inhibition.