1. Conventional intracellular recordings were made from rabbit nodose neurones in vitro. Prostaglandins D2 and E2, but not F2 alpha, produced a selective, concentration-dependent (1-100 nM) inhibition of a slow, Ca2+-dependent spike after-hyperpolarization (a.h.p.). Block of the slow a.h.p. was accompanied by an increased membrane resistance and a small (less than 10 mV) depolarization of the membrane potential. Inhibition of the slow a.h.p. produced no change in the voltage-current relationship other than the increased membrane resistance. 2. In C neurones with slow a.h.p.s, trains of brief depolarizing current pulses (2 ms duration, 0.1-10 Hz) could not elicit repetitive action potentials without failure at rates above 0.1 Hz. By contrast, C neurones without slow a.h.p.s could respond at stimulus frequencies up to 10 Hz. The frequency-dependent spike firing ability of slow a.h.p. neurones was eliminated by inhibition of the slow a.h.p. 3. Action potentials were also evoked by intrasomatic injection of paired, depolarizing current ramps (1 nA/10 ms, 0.1-5 s inter-ramp interval). For neurones without a slow a.h.p., the current threshold and number of evoked spikes were the same for both ramps, and the ramps were nearly superimposable. In neurones with a slow a.h.p., the current threshold for the first spike in the second ramp was greatly increased (300-500%) and the number of evoked spikes was reduced. Following inhibition of the slow a.h.p., the current threshold and number of evoked spikes was the same for both ramps. 4. Forskolin, a direct activator of the catalytic subunit of adenylate cyclase, also produced a concentration-dependent inhibition of the slow a.h.p., with 50% block at 30 nM. Prostaglandin D2 and forskolin produced identical enhancement of excitability in C neurones and neither substance produced any effect on C neurones that could not be attributed to inhibition of the Ca2+-dependent K+ conductance associated with the slow a.h.p. We propose that, in some visceral sensory neurones, the level of excitability is regulated by cyclic AMP-mediated control of the slow a.h.p.