Tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) are products of activated monocytes/macrophages with anti-tumor activity. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) is a potent monocyte/macrophage activator. Sera from cats after intravenous L-MTP-PE administration showed TNF alpha activity using a WEHI-164 cell cytotoxicity assay and IL-6 activity using an IL-6 dependent mouse 7TD1 hybridoma cell proliferation assay. Serum TNF alpha activity peaked at 2 hours after L-MTP-PE administration. Significant differences from lipid-equivalent controls were observed at 2 and 3 hours (P < 0.05). Neutralization of serum TNF alpha activity was accomplished with serial dilutions of rhTNF alpha monoclonal antibody. Serum IL-6 activity peaked at 3 hours after L-MTP-PE administration. Significant differences from lipid-equivalent controls were observed at 2, 3, and 4 hours (P < 0.05). Neutralization of serum IL-6 activity was not achieved with goat anti-rhIL-6 polyclonal antibody. Intravenous L-MTP-PE, but not lipid-equivalent, induces serum TNF alpha and IL-6 activity in normal cats.