Background&Aim: The extent to which gut motility and smooth muscle contractility are altered by intestinal inflammation depends on the nature of the underlying immune activation. The muscarinic receptor on smooth muscle plays a critical role in mediating acetylcholine-driven motor function. We examined the ability of cytokines to influence muscarinic receptor characteristics on intestinal longitudinal muscle, and relate the findings to studies on carbachol-induced contraction. Methods: Cells were isolated from longitudinal muscle myenteric plexus (LMMP). Cytokine receptor expression, muscle contractility, and muscarinic agonist receptor characteristics by agonist displacement of [N-methyl-³H] scopolamine ([³H] NMS) binding were examined. Results: The TGF-1 (543bp) and the IFN- receptor-1 (660bp) receptors were identified on smooth muscle cells. Scatchard analysis revealed dissociation constant (K_D) and maximum binding (B_max) values for [³H]NMS of 2.6nM and 2.4 x 10⁴ sites/cell, respectively in control cells. Nematode infection was accompanied by a reduction in inhibitory constant of the high affinity sites (K_H) and this was independent of signal transduction and activator of transcription (STAT)6. Preincubation with TGF-1 enhanced longitudinal muscle contractility, and decreased the K_H to 2.2pM (increased muscarnic receptor affinity) whereas preincubation with IFN- increased the K_H to 0.4µM (decreased muscarinic receptor affinity) and decreased longitudinal muscle contractility. Preincubation of LMMP with interleukin (IL)-13 decreased the K_H to 0.2nM. Conclusions: Cytokines exert differential effects on the muscarinic receptor on intestinal longitudinal smooth muscle. These findings explain the basis for altered muscle contractility observed in Th1 and Th2 models of inflammation, as well as in the post nematode-infected state.