The introduction of light emitting diode (LED) devices as a novel treatment for pain relief in place of low-level laser warrants fundamental research on the effect of LED devices on one of the potential explanatory mechanisms: peripheral neurophysiology in vivo. A randomised controlled study was conducted by measuring antidromic nerve conduction on the peripheral sural nerve of healthy subjects (n=64). One baseline measurement and five post-irradiation recordings (2-min interval each) were performed of the nerve conduction velocity (NCV) and negative peak latency (NPL). Interventional set-up was identical for all subjects, but the experimental group (=32) received an irradiation (2 min at a continuous power output of 160 mW, resulting in a radiant exposure of 1.07 J/cm(2)) with an infrared LED device (BIO-DIO preprototype; MDB-Laser, Belgium), while the placebo group was treated by sham irradiation. Statistical analysis (general regression nodel for repeated measures) of NCV and NPL difference scores, revealed a significant interactive effect for both NCV (P=0.003) and NPL (P=0.006). Further post hoc LSD analysis showed a time-related statistical significant decreased NCV and an increased NPL in the experimental group and a statistical significant difference between placebo and experimental group at various points of time. Based on these results, it can be concluded that LED irradiation, applied to intact skin at the described irradiation parameters, produces an immediate and localized effect upon conduction characteristics in underlying nerves. Therefore, the outcome of this in vivo experiment yields a potential explanation for pain relief induced by LED.