We have compared the analgesic efficacy of the racemic mixture and the stereoisomer (S+) of the NMDA antagonist ketamine. In a double-blind, three-way crossover, placebo-controlled study, we assessed the following: pain evoked by small/large area pressure stimuli, pain detection threshold and pain ratings to small/large area of heat stimuli, pain detection threshold and pain rating to heat stimuli of brief/long duration, summation pain threshold and pain ratings to repeated heat/electrical stimuli, side effects and reaction time. Plasma concentrations of 350 ng ml-1 for ketamine (racemic) and 180 ng ml-1 for ketamine (S+) were tried. We found that ketamine (racemic) prolonged the reaction time more than ketamine (S+). Both drugs affected pain caused by repeated stimuli or stimuli of long duration equally or more than a single stimulus of short duration. They also affected pain evoked from large areas equally or more than pain evoked from small areas. The (S+)-isomer was approximately twice as potent as the racemic mixture of ketamine in inhibiting central summation.