There are two cyclooxygenase (Cox) genes encoding characterised enzymes, Cox-1 and Cox-2. Non-steroidal anti-inflammatory drugs are commonly used as analgesics in inflammatory arthritis and these often inhibit both cyclooxygenases. Recently inhibitors of Cox-2 have been used in the treatment of inflammatory arthritis, as this isoform is thought to be critical in inflammation and pain. The objective of this study was to determine the effect of Cox-1 or Cox-2 gene disruption on the development of chronic Freund's adjuvant-induced arthritis and inflammatory pain in male and female mice. The effect of Cox-1 or Cox-2 gene disruption on inflammatory hyperalgesia, allodynia, inflammatory oedema and arthritic joint destruction was studied. Cox-2 knockout mice (Cox-2 -/-) showed reduced oedema and joint destruction in female, but not male animals. In addition, neither male nor female Cox-2 -/- mice developed thermal hyperalgesia, or mechanical allodynia, either ipsilateral or contralateral to the inflammation. Cox-1 gene disruption also reduced inflammatory oedema and joint destruction in female, but not male mice, although females of both Cox -/- lines did show some bony destruction. There was no difference in ipsilateral allodynia between Cox-1 knockout and wild type animals, but female Cox-1 -/- mice showed reduced contralateral allodynia compared to male Cox-1 -/- or wild type mice. These data show that the gene products of both cyclooxygenase genes contribute to pain and local inflammation in inflammatory arthritis. There are sex differences in some of these effects, and this suggests that the effects of cyclooxygenase inhibitors may be sex dependent.