Transcutaneous electrical nerve stimulation (TENS) is commonly used for pain relief. However, little robust research exists regarding the combination of parameters required to provide effective doses. This study investigated the hypoalgesic effects of different parameter combinations, applied simultaneously at two sites (segmental and extrasegmental), on pressure pain threshold (PPT) in pain-free humans. Two-hundred and eight volunteers (median age 22 years, range 20–26) were randomized to eight groups: six active TENS groups, placebo and control. Parameter combinations were such that frequency always differed at each site (110Hz or 4Hz), but intensity could be either the same or different levels: high (to tolerance without pain) or low (strong but comfortable). TENS was administered to the forearm over the radial nerve and the ipsilateral leg below the fibular head for 30min with monitoring for 30 further minutes. PPT measurements were taken bilaterally from the mid-point of first dorsal interosseous muscle, by an independent blinded rater, at baseline and at six subsequent 10-min intervals. Log-transformed data were analysed using repeated-measures analysis of covariance (baseline values and gender as covariates). Those groups using high-intensity stimulation at the segmental stimulation sites showed significantly greater hypoalgesia than placebo (p<0.025 in each case). The largest hypoalgesic effect was for simultaneous high-intensity stimulation at segmental and extrasegmental sites, using different frequencies. These results reaffirm that high-intensity stimulation (regardless of frequency) is of fundamental importance in effective dosage.