Depolarization and reduction in the C fibre compound action potential (C spike) in response to 5-HT were recorded simultaneously from rabbit isolated vagus nerve. 5-HT (0.1-100 mumol/l) was applied either as single concentrations or cumulatively and EC50 and IC50 values measured from individual concentration-response curves. The EC50 values for depolarization (cumulative curves: 2.33, 1.64-3.33 mumol/l, geometric means and 95% confidence limits, n = 31; non-cumulative curves: 3.99, 2.89-5.52 mumol/l, n = 9) were significantly higher than IC50 values for C spike reduction (cumulative curves: 1.25, 0.91-1.74 mumol/l, n = 30; non-cumulative curves: 1.41, 0.72-2.76 mumol/l, n = 8). Complex effects on the C spike were observed, suggesting a susceptible group of C fibres and a 5-HT-resistant component to the C fibre action potential. The motor nerve C fibres in the vagus nerve appear insensitive to 5-HT, whereas the sensory C fibres were sensitive to 5-HT. Phenylbiguanide had a similar selective effect on the C spike, while the depolarizing agents, 1,1-dimethyl-4-phenylpiperazinium (DMPP) and gamma-aminobutyric acid (GABA) did not. Cumulative concentration-response curves for depolarization and C spike reduction could be repeated reproducibly if an interval of 90 min was left between determinations. Up to 6 curves could be generated from one preparation. The 5-HT uptake inhibitor, citalopram (0.1 and 1 mumol/l), had no effect on cumulative concentration-response curves.(ABSTRACT TRUNCATED AT 250 WORDS)