Transcutaneous electrical nerve stimulation (TENS) is a popular form of electrostimulation. Despite an extensive research base, there remains no consensus regarding the parameter selection required to achieve maximal hypoalgesic effects. The aim of this double blind, sham-controlled study was to investigate the relative hypoalgesic effects of different TENS parameters (frequency, intensity and stimulation site) upon experimentally induced mechanical pain. Two hundred and forty participants were recruited in order to provide statistical analysis with 80% power at alpha = 0.05. Subjects were randomised to one of the six TENS groups, a control, and a sham TENS group (n = 30, 15 males, 15 females, per group). TENS groups differed in their combinations of stimulation; frequency (4 or 110 Hz), intensity ('to tolerance' or 'strong but comfortable') and stimulation site (segmental--over the distribution of the radial nerve or, extrasegmental--over acupuncture point 'gall bladder 34', or a combination of both segmental and extrasegmental). Pulse duration was fixed at 200 micros. Stimulation was delivered for 30 min and subjects were then monitored for a further 30 min. Mechanical pain threshold (MPT) was measured using a pressure algometer and taken from the first dorsal interosseous muscle of the dominant hand, ipsilateral to the stimulation site. MPT measures were taken, at baseline, and at 10-min intervals for 60 min. Difference scores were analysed using repeated measures and one-way ANOVA and relevant post hoc tests. Low frequency, high intensity, extrasegmental stimulation produced a rapid onset hypoalgesic effect, which increased during the stimulation period (P <0.0005 control and sham) and was sustained for 30 min post-stimulation (P <0.0005(control), P = 0.024(sham)). Whilst high frequency, 'strong but comfortable' intensity, segmental stimulation produced comparable hypoalgesic levels during stimulation, this effect was not sustained post-stimulation. Stimulation at a combination of the two sites did not produce any greater hypoalgesic effects. These results may have implications for the clinical use of sensory stimulation.