We studied the effects of two non-steroidal anti-inflammatory analgesics (NSAIAs), acetylsalicylic acid (ASA) and acetaminophen, on sleep patterns in rats with adjuvant-induced arthritis. We found that in the normal rat both NSAIAs reduced non-rapid eye movement (NREM) sleep. In arthritic rats ASA and acetaminophen had opposite effects on sleep. ASA increased wakefulness and decreased all sleep stages and acetaminophen decreased wakefulness and increased NREM sleep and paradoxical sleep during the light hours (the hours of maximal sleep in the normal rat). When the effects of severity of arthritis were factored out, both drugs still had large and significant effects on sleep and wakefulness. Thus, two prostaglandin synthetase inhibitors showed differential effects on sleep and wakefulness in the normal rat and in rats experiencing chronic pain. Although ASA is important in the treatment of pain in rheumatic diseases, it may contribute to abnormal sleep patterns.