1. This study was performed to elucidate the role of prostaglandins in the action of bradykinin on serosal afferent neurones sup-plying the rat jejunum. Extracellular recordings of multiunit activity were made from serosal afferents in isolation, using a novel in vitro preparation. The discharge of single afferents within the multi-unit recording was monitored using waveform discrimination software. 2. All afferents tested were both mechano- and capsaicin sensitive. Application of bradykinin elicited increases in whole nerve discharge in a concentration-dependent manner. The agonist potency estimate (EC50) was 0.62 +/- 0.12 mu M and is consistent with an interaction at the B-2 receptor subtype. 3. The stimulatory effect of bradykinin on serosal afferents was antagonized by a specific antagonist of the B-2 receptor, HOE140. In contrast, a selective B-1 receptor antagonist, [des-Arg(10)]HOE140, had no effect. The IC50 estimate obtained for HOE140 was 1.6 nM and again consistent with an interaction at B-2 receptors. 4. The response to a submaximal concentration of bradykinin (1 mu M) was significantly reduced to 24.4 +/- 54.9% of control following blockade of cyclo-oxygenase activity with naproxen (10 mu M). The addition of 1 mu M prostaglandin E-2 (PGE(2)), in the presence of naproxen, had no direct effect on afferent activity, but fully restored the response to bradykinin in 15 single a,afferents. 5. In summary bradykinin stimulates serosal afferents by a direct action on kinin B-2 receptors that are present on serosal afferent terminals. The response to bradykinin is dependent on the presence of prostaglandins, particularly PGE(2). We suggest that bradykinin has a self-sensitizing action, whereby it stimulates the release of PGE(2), which in turn sensitizes the endings of serosal afferent neurones responsive to bradykinin.