The therapeutic effect of aspirin and the other nonsteroidal anti-inflammatory drugs derives from the peripheral inhibition of prostaglandin synthetase. Aspirin produces irreversible inhibition, whereas the inhibition triggered by the other nonsteroidal anti-inflammatory drugs is reversible. Despite proved analgesic efficacy, use of aspirin and the nonsteroidal anti-inflammatory drugs may be accompanied by a wide range of side effects of a potentially serious nature. For relief of pain, there appears to be no clear-cut superiority of one nonsteroidal anti-inflammatory drug over another, and patients who fail to respond to one class of nonsteroidal anti-inflammatory drugs may respond to a representative of another class. As with aspirin, it is difficult to demonstrate the superiority of higher doses of these agents over the lower doses. The side-effect profile of non-narcotic analgesics favors acetaminophen, presumably because its inhibition of prostaglandin synthetase occurs centrally. Acetaminophen does not appear to have the same potential for toxicity that is seen with aspirin and other nonsteroidal anti-inflammatory drugs. At dosages up to 4 g per day, acetaminophen compares favorably in analgesic potency to aspirin and other nonsteroidal anti-inflammatory drugs, and it should be considered the treatment of choice for mild-to-moderate pain. Safe conditions for the analgesic use of nonsteroidal anti-inflammatory drugs in children and pregnancy have not been established. Because it is virtually free of side effects, acetaminophen may be the mild analgesic of choice for the pregnant patient. It has been used safely for years in children. Only a limited number of analgesic studies have been conducted in children. The results of analgesic studies carried out in adults are generally recognized as applicable to pain relief in children.