We have studied experimentally induced itch (using histamine iontophoresis) and pain (using topical mustard oil) in healthy human volunteers, measured using visual analogue scale (VAS) ratings. The effects of the following counterstimuli were evaluated: innocuous vibration; innocuous transcutaneous electrical nerve stimulation (TENS); innocuous warming of skin; noxious heating of skin; noxious chemical skin stimulation (using mustard oil); mildly noxious constant current transdermal electrical stimulation. Innocuous stimuli applied 2 min after histamine or mustard oil challenge produced a modest reduction of itch and pain ratings (20-30%), which did not persist for more than 20 sec when the counterstimuli were removed. These changes may well be due to distraction. The same stimuli (in some cases applied for periods of up to 1 h) given prior to the histamine or mustard oil, produced no significant reduction in evoked itch or pain. Noxious stimuli of all types applied 2 min after histamine or mustard oil challenge produced a consistent and significant inhibition of itch (22.8-52.7%) which outlasted the period of counterstimulation application. In contrast, these stimuli had no significant effects on chemically induced pain. The anti-pruritic state produced by brief noxious stimuli were effective for periods of more than 30 min. The differential effects of noxious counterstimuli on itch and pain do not support the suggestion that itch is a subliminal form of pain. Noxious counterstimuli are likely to act via a central rather than peripheral mechanism. The novel finding that a persistent anti-pruritic state can be induced by transdermal constant current may be useful in conditions of clinical itch.