A reduction of extracellular pH activates an inward current in nociceptors (Krishtal et al. 1980). One condition associated with tissue acidosis is inflammation, where the pH can drop to pH 5.4 (Steen et al. 1992). During the inflammatory process numerous mediators are released, including arachidonic acid (AA). It has been demonstrated that AA enhances proton-gated currents in cerebellar Purkinje neurones (Allen et al. 2002). Here we provide evidence that AA potentiates both proton-gated currents in dorsal root ganglia (DRG) neurones and the inward membrane current carried by an acid gated ion channel ASIC). Neonatal Wistar rats (3 – 10 days old) were killed by cervical dislocation followed by decapitation. Proton-gated currents in DRG neurones and ASIC1a transfected CHO cells were examined using the whole-cell patch clamp method. Data are presented as mean±S.E.M. Application of a pH 6.3 solution evoked three distinct inward currents in different DRG neurones: a slowly inactivating transient current (amplitude -2.57±0.4 nA, time constant of inactivation 2.99±0.25 sec, n = 52), a biphasic current (rapidly inactivating transient phase = 1.48±0.16 nA, time constant of inactivation 0.30±0.02 sec, sustained phase = 0.058±0.01 nA, n = 34) and a pure sustained current (0.072±0.018 nA, n = 17). The different inactivation times for the transient current and transient phase of the biphasic current (P < 0.0001, Student's t test) suggest different proton-gated ion channels may produce them. The sustained phase of the biphasic current has a similar amplitude to the pure sustained current suggesting the same ion channel(s) could produce them. Addition of 10μM AA to the extracellular solution potentiated peak responses for all three currents: transient 122.6±4.4 % of control (P < 0.01, paired t test, n = 7), biphasic 171.3±18.5 % of control (P < 0.05, n = 6) and sustained 263.6±48.3 % of control (P < 0.05, n = 7). To investigate the contribution of ASIC1a to the potentiating effect of AA, ASIC1a was transfected into CHO cells where 1μM AA was found to significantly potentiate the response to pH 6.3 solution (288.5±43.9 % of control, P < 0.01, n = 6). These data suggest that enhancement of acid mediated pain in inflammation can arise from potentiation of ASIC mediated proton-gated currents by AA. Further experiments will focus on the mechanism of action of AA.