Although Transcutaneous Electrical Nerve Stimulation (TENS) has become a popular modality in pain management over the past 20 yr, there is still debate over its mechanisms of action and the precise relevance of stimulation parameters to its hypoalgesic effects. Thus, confusion still surrounds the selection of optimal stimulation parameters. Two separate studies (total n=88) were carried out to investigate the effect of four combinations of TENS pulse durations (50 (µ.s & 200 µ.s) and frequencies (4 Hz and 110 Hz) on nerve conduction in the human superficial radial nerve and on Mechanical Pain Threshold (MPT) within the associated sensory distribution of the nerve over the dorsum of the hand. Results showed that application of one combination of TENS parameters (110 Hz, 200 µ,s) directly over the course of the nerve produced a significant increase in both peripheral nerve conduction latency (P< 0.05; analysis of variance (ANOVA)) and MPT (P< 0.01). In addition, there was a high correlation (r=0.9) between shifts in MPT and negative peak latency for the groups treated with this combination of TENS parameters. The results of this study thus illustrate that combinations of TENS parameters are important to the peripheral neurophysiological effects of this modality and, further, its associated hypoalgesic effects, at least on the model of pain used here.