Background: Substance P (SP) is increased in the inflamed intestine of Trichinella spiralis-infected rats, but the underlying mechanism is unknown. Interleukin 1β (IL-1β) messenger RNA and protein is expressed in the longitudinal muscle-myenteric plexus (LM-MP) of this model. Thus, the purpose of the study was to examine the ability of human recombinant IL-1β (hrIL-1β) to increase SP in LM-MP preparations from the intestine of noninfected rats. Methods: LM-MP preparations were incubated with hrIL-1β, and immunoreactive SP (IR-SP) was assessed in the tissues by radioimmunossay or immunohistochemistry. Results: hrIL-1β increased IR-SP in the tissue in a time- and concentration-dependent manner, being maximal after 6 hours at a concentration of 10 ng/mL. The IR-SP could be depleted by scorpion venom, and immunohistochemistry revealed increased staining for SP within nerves of the LM-MP. The action of IL-1β was dependent on protein synthesis, was receptor mediated, and was not due to endotoxin contamination of the cytokine preparation. Conclusions: hrIL-1β stimulates the synthesis of SP in myenteric nerves of rat intestine.