The authors challenge the general view that the analgesic effect of the nonsteroidal anti-inflammatory drugs (NSAIDs) can be universally attributed to their inhibitory effects on the synthesis of peripherally formed prostaglandins. Analgesic activity by some of these compounds in the reduction of physiological pain elicited by a single noxious stimulus, or the treatment of acute pain which results from sudden trauma to otherwise healthy tissue, is better described as an antinociceptive effect. Single-dose studies in the dental pain model that have been conducted in double-blind conditions and included a placebo control group have been reviewed; those NSAIDs which are significantly superior to the reference compound aspirin 650mg and those which could represent real alternatives to the use of narcotics in certain situations for the management of acute pain have been identified. Azapropazone, diflunisal, naproxen, oxaprozin and tolmetin are all weak inhibitors of prostaglandin synthesis, yet they have been shown to be more effective than aspirin. In a model of joint pain, azapropazone 600mg has been shown to be as effective as pethidine (meperidine) 100mg despite being the weakest inhibitor of prostaglandin synthesis. Whether the antinociceptive effect of azapropazone acts at a peripheral or a central level, or both, is not clear; evidence for the effects of NSAIDs on the central nervous system (CNS) is discussed. Historically, the antinociceptive character of some NSAIDs is apparent in several studies in both animals and humans. More recently, experimental algesimetry models designed to distinguish the antinociceptive effects of NSAIDs include the use in humans of photoplethysmography and computer-supported infrared thermographic imaging.