Quantitative analysis of the effects of amitriptyline on nicotine-induced (10 µM) increases in excitability and the amplitude and latency to onset of the C-fibre compound action potential (CAP) response to supra-maximal stimulation. In concentrations from 1 to 10 µM, amitriptyline reduced, concentration-dependently, the nicotine-induced (10 µM) increase in excitability in unmyelinated human axons. An EC50 for this effect of 2.6 ± 0.2 µM was calculated. In addition, in concentrations above 1 µM, amitriptyline concentration-dependently reduced the amplitude and increased the latency to half-maximum amplitude of the C-fibre CAP. However, these changes are much less prominent than the reduction of the nicotine-induced increase in axonal excitability observed in the presence of amitriptyline.