We examined the analgesic effect of racemic ketamine and its 2 enantiomers in 16 female patients (age: 20-29 years) suffering acute pain after oral surgery and in 7 female patients (age: 42-79 years) suffering chronic neuropathic orofacial pain. All 3 forms of ketamine consistently relieved postoperative pain, (S)-ketamine being 4 times more potent than (R)-ketamine. The analgesic effect was maximal 5 min after i.m. injection and lasted for about 30 min. The 7 patients with neuropathic pain received ketamine at one or several occasions. Four patients (age: 54-79 years) who had suffered pain for more than 5 years did not experience an analgesic effect, whereas 3 patients (age: 42-53 years) who had suffered pain for less than 3 years reported pain relief lasting from 24 h to 3 days. The individual type of response did not depend on the form of ketamine used. The mental side effects were qualitatively similar for the 3 forms of ketamine. Relative to the analgesic effect (S)-ketamine caused more disturbing side effects than did (R)-ketamine. The mean serum concentration of each form of ketamine at the time of maximal effect was close to the approximate Kd value for PCP site occupancy by that particular form. This is in concert with the hypothesis that the effect of ketamine on acute nociceptive pain is due to N-methyl-D-aspartate (NMDA) receptor inhibition and adds to the evidence that NMDA receptors are important for the perception of acute, nociceptive pain in humans.(ABSTRACT TRUNCATED AT 250 WORDS)