Since peritonitis remains a serious clinical problem, we have evaluated the prophylactic efficacy of intraperitoneally administered chemotactic substances in murine intraperitoneal infections. The injection of 10 ml of 3% thioglycollate increased the peritoneal white blood cell count of rats from 1.3 +/- 0.1 X 10(6) (mean +/- SEM) to 1.1 +/- 0.1 X 10(7) (mean +/- SEM) cells/ml. This increase in the number of intraperitoneal phagocytes resulted in reduction in mortality caused by an inoculum consisting of E. coli and hemoglobin from 68% in the control group to 29% in the thioglycollate pretreated group (p less than or equal to 0.02). Intraperitoneal injection of N-formyl-methionyl-phenylalanine (FMP), a chemotactically active oligopeptide, increased the intraperitoneal granulocyte count from virtually 0 to 1 X 1.9 +/- 0.53 X 10(4) (mean +/- SEM) cells/ml after 90 minutes. The rats pretreated in such a manner showed a mortality of 51% after an intraperitoneal challenge with an E. coli/hemoglobin inoculum as compared to a mortality of 72% in control animals (p less than or equal to 0.025). Thus, chemotactic substances can effectively increase the number of phagocytes and concurrently induce resistance to an intraperitoneal bacterial challenge.