Vasoactive intestinal polypeptide (VIP), located within intrinsic neurones of the guinea-pig taenia coli, has been proposed as a neurotransmitter which may mediate certain non-adrenergic, non-cholinergic effects within the gastrointestinal tract. The relaxation of the taenia coli produced by exogenous VIP has a longer latency and time to maximum than the relaxation which is obtained during electrical stimulation of the non-adrenergic, non-cholinergic nerves. The responses to exogenous VIP (0.03-1 microM) were abolished by the proteolytic enzyme alpha-chymotrypsin (1 U/ml), whereas there were no statistically significant changes in the inhibitory responses to intramural nerve stimulation (0.1-5 Hz) or exogenous ATP (0.03-100 microM), which closely mimics the nerve-mediated response. Apamin is a neurotoxin which prevents the increase in K+ conductance associated with the inhibitory junction potential produced by stimulation of the non-adrenergic, non-cholinergic inhibitory nerves. In the presence of apamin (0.005-1 microM) the responses to intramural nerve stimulation and exogenous ATP were significantly antagonised, and often converted to contractile responses. The VIP-induced relaxations during apamin treatment were not significantly decreased. These results suggest that VIP is unlikely to be the transmitter released from the non-adrenergic, non-cholinergic nerves of the guinea-pig taenia coli, and are consistent with the view that these nerves are purinergic in nature.