The aims of this study were: (1) to test the hypothesis of a central analgesic effect of the aspirin-like drug ketoprofen and (2) to attempt to differentiate between a spinal and a supraspinal mechanism in this possible central action. The threshold of the nociceptive flexion reflex from the biceps femoris muscle elicited by sural nerve stimulation was studied before and after a double-blind, cross-over and randomized intravenous injection of ketoprofen (100 mg in 5 ml saline) and saline (5 ml) in 2 groups of volunteers. The first one was composed of 10 normal subjects while the second consisted of 8 paraplegic patients with complete spinal section of traumatic origin. In normal subjects, ketoprofen injection resulted in a rapid and significant increase (+68%) of the threshold of the nociceptive reflex, while saline injection produced a slow increase of only 17% of this threshold. In contrast, in paraplegic patients, neither ketoprofen nor saline produced any significant change in the nociceptive reflex threshold. A supraspinal involvement in the central analgesic effect of this drug is discussed.