The possible involvement of nitric oxide (NO) in non-adrenergic nerve-mediated relaxations of guinea-pig gastrointestinal smooth muscle was investigated using longitudinal muscle that lies between the taenia of the caecum. Relaxations induced by electrical field stimulation in this preparation are similar to those described in other preparations of guinea-pig intestinal muscle when enteric inhibitory neurons are stimulated; they were blocked by tetrodotoxin (10(-6) M) but were unaffected by guanethidine (10(-6) M). N-Nitro-L-arginine (NOLA) (5 x 10(-5) to 10(-4) M), an inhibitor of NO synthase, and haemoglobin (10(-5) M), which reduces bioavailability of NO, both reduced the amplitude of nerve-mediated relaxations to less than 50%, without affecting the ability of the muscle to relax. These results suggest that NO may play a role in inhibitory neurotransmission to this preparation.