Colonic inflammation was produced in rats and mice by peptides chemotactic for polymorphonuclear leukocytes. Instillation of formylmethionyl-leucyl-phenylalanine (FMLP) and formylnorleucyl-leucyl-phenylalanine (FNLP) into isolated segments of rat colon caused marked mucosal edema and polymorphonuclear leukocyte infiltration within 2 hours. Higher concentrations of FNLP caused ulceration and necrosis as well. Formylmethionine (FMet), a compound with less chemotactic activity, caused much less inflammation. In mice, rectal instillation of FNLP caused dose-dependent acute mucosal inflammation which persisted for longer than 12 hours. Twice-weekly rectal instillation of FNLP provided a model of colitis based on neutrophil chemotaxis.