Macrophage procoagulant activity (PCA) has been proposed as a critical element in the formation of intra-abdominal abscesses. We tested the ability of local and systemic lipids (a known PCA inhibitor in vitro) to alter both peritoneal macrophage PCA and mixed Escherichia coli/Bacteroides fragilis intra-abdominal abscess formation in vivo. Lipids given intraperitoneally inhibited measured inducible peritoneal macrophage PCA for 8 h, and, in other animals, significantly decreased the number of abscesses formed and prevented abscesses in 29% of animals. Parallel experiments using subcutaneous intralipids did not show these effects. These results support the hypothesis that macrophage PCA produced locally is critical for intraperitoneal abscess formation.