Murine Schistosomiasis mansoni is a parasitic disease in which granulomas develop around the schistosome ova that lodge in the liver and intestines of the host. The granuloma eosinophils make substance P (SP), a cytokine with immunoregulatory properties. Within the granuloma SP can modulate IFN-gamma production through interaction with a substance P-like receptor. SP belongs to a family of hormones called tachykinins. Three mammalian tachykinins are SP, neurokinin A (substance K), and neurokinin B (neuromedin K). In humans and rats, there are at least three distinct tachykinin receptors designated NK-1, NK-2, and NK-3. The NK-1 receptor binds only SP with high affinity. Using reverse transcription-PCR, cDNA cloning, and sequence analysis, we showed that granulomas isolated from the liver of infected mice express an authentic SP (NK-1) receptor but have no detectable neurokinin A (NK-2) and neurokinin B (NK-3) receptor mRNA, as determined by PCR. CD4+ granuloma T lymphocytes, purified by FACS, express NK-1 receptor mRNA. Normal liver devoid of granulomas exhibited none of the three tachykinin receptor subclasses.