The P(2)-purinoceptor antagonist, suramin, was used to investigate the possible involvement of adenosine 5'-triphosphate (ATP) in the inhibitory non-adrenergic non-cholinergic (NANC) innervation of the rat gastric fundus. ATP (1-30 microM) produced biphasic responses consisting of concentration-dependent relaxations followed by concentration-dependent contractions. Suramin (200 microM) significantly reduced relaxations and abolished contractions to ATP. Under NANC conditions, electrical field stimulation (EFS) induced frequency-dependent relaxations. Suramin (200 microM) and the peptidase alpha-chymotrypsin (1 u ml(-1)) had the same effects on EFS-induced relaxations: their duration was reduced, but their magnitude was unaffected. Cumulative relaxations to vasoactive intestinal peptide (VIP; 0.1-100 nM), and to the VIP analogue pituitary adenylate cyclase activating peptide 1-27 (PACAP; 0.2-100 nM), were almost completely abolished by alpha-chymotrypsin (1 u ml(-1)), and were inhibited by suramin (3-200 microM) in an apparently competitive manner. Schild plot analysis indicated that suramin had pA(2) values of 5.1+/-0.2 (Hill slope=0.9+/-0.2) and 5.6+/-0.1 (Hill slope=1.0+/-0.1), against VIP and PACAP, respectively. Concentration-dependent relaxations to nitric oxide (1-30 microM) and cumulative relaxations to isoprenaline (0.1-300 nM) were not affected by suramin (200 microM). No conclusions can be made regarding the possible involvement of ATP in EFS-induced NANC relaxations. The results suggest that suramin acts as a competitive antagonist at VIP receptors in the rat gastric fundus.