We examined the effect of the subcutaneous infiltration of ketamine, lidocaine and saline before injury on capsaicin-induced pain and hyperalgesia. Twelve healthy volunteers participated in two separate, randomized, double-blind, placebo-controlled crossover experiments. In experiment 1, 100 micrograms capsaicin was injected intradermally in one volar forearm 10 min after the skin had been pretreated with lidocaine 20.0 mg in 2.0 ml or 0.9% saline 2.0 ml at the capsaicin injection site. In experiment 2, a similar capsaicin test was given 10 min after the skin had been pretreated with ketamine 5 mg in 2.0 ml or 0.9% saline 2.0 ml. To control for possible systemic effects, the capsaicin injection site was pretreated by injection of saline into the skin and the contralateral arm was treated with active drug, and vice versa. Outcome measures were spontaneous pain, pain evoked by punctate and brush stimuli, and areas of brush-evoked and punctate-evoked hyperalgesia. Lidocaine reduced all measures compared with placebo (P < 0.001), whereas ketamine failed to change any measures. Pain scores and areas of hyperalgesia were not affected when the contralateral site was infiltrated with ketamine or lidocaine. Lidocaine produced no side-effects, whereas ketamine produced paraesthesia, dizziness and sleepiness in six out of 24 (25%) cases. Blocking peripheral sodium channels with locally administered lidocaine reduces spontaneous pain and capsaicin-induced hyperalgesia but local block with the NMDA-type glutamate receptor antagonist ketamine has no effect on capsaicin-induced pain and hyperalgesia.