1. The aim of the present study was to investigate whether the guinea-pig small intestine shows accommodation to infused fluid, similarly to other regions of the gastrointestinal tract. Tetrodotoxin, papaverine and transmitter antagonists were used to establish the existence of reflex pathways and the nature of the neurotransmitters involved. 2. Compliance, measured as the change in volume of infused fluid divided by the intraluminal pressure change, was reduced by tetrodotoxin (0.6 microM), indicating that there is an overall neurally mediated relaxation of the circular muscle in response to low rates of distension. Papaverine (10 microM) did not have any significant effect on compliance at the low rates of distension, suggesting that the circular muscle is fully relaxed. 3. At each rate of distension, 400 microM N omega-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) significantly decreased the compliance of the intestinal wall, indicating that the circular muscle was relaxed by a nitric oxide-mediated mechanism. Apamin (0.5 microM), which blocks a component of inhibitory transmission, did not have a significant effect. 4. In control preparations, the intestinal wall was less compliant when distended by fluid at a fast rate, compared with the lower rates of distension. This was not due to changes in passive components of the intestinal wall or a myogenic response to rapid stretch. 5. When the intestine was distended rapidly, 1 microM hyoscine and 100 microM hexamethonium increased intestinal compliance. However, they had no detectable effect on compliance with low rates of distension.(ABSTRACT TRUNCATED AT 250 WORDS)