The guinea pig rectum, but not colon, is innervated by a specialized class of distension-sensitive mechanoreceptors which have transduction sites corresponding to rectal intraganglionic laminar endings (rIGLEs). Rectal mechanoreceptors recorded in vitro, had low threshold to circumferential stretch, adapted slowly and could respond within 2 ms to mechanical stimulation by a piezo-electric probe. Antagonists to ionotropic NMDA (CGS 19755, memantine) and non-NMDA (DNQX) glutamate receptors did not affect mechanotransduction. In normal Krebs solution, the P2X purinoreceptor agonist, ,-methylene ATP reduced mechanoreceptor firing evoked by distension, but simultaneously relaxed circular smooth muscle and inhibited stretch-induced contractions. Neither ATP nor ,-methylene ATP affected mechanotransduction when transduction sites were directly compressed with von Frey hairs. The P2 purinoreceptor antagonist, PPADS did not affect stretch-induced firing but reduced the inhibitory effect of ,-methylene ATP on stretch-induced firing. Under isometric condition, blocking synaptic transmission in Ca²⁺-free solution reduced stretch-evoked firing but not when basal tension was restored to control levels. Under isotonic condition, Ca²⁺-free solution did not significantly affect load-evoked firing. The blockers of mechano-gated and/or TRP channels, benzamil, Gd³⁺, SKF 96365 and ruthenium red inhibited stretch-induced firing but, in parallel, significantly reduced stretch-induced contractions. Benzamil and SKF 96365 were able to inhibit mechanotransduction when transduction sites were compressed with von Frey hairs. The results show that mechanotransduction is rapid but does not depend on fast exocytotic release of mediators. It is likely that stretch-activated ion channels on rIGLEs are involved in direct, physical mechanotransduction by rectal low threshold mechanoreceptors.