This study evaluated the effects of systemic indomethacin on carrageenin evoked c-Fos expression in rat lumbar spinal cord neurons. Fos-like immunoreactivity was not observed after the intraplantar injection of the control vehicle saline. 2 h after administration of carrageenin (6 mg/150 microliters) into the hind limb, Fos-like immunoreactive neurons were observed in the lumbar spinal cord (64 labelled neurons per L4-L5 sections) and were numerous in the superficial laminae (I-II), whereas at 3-4 h both superficial and deeper laminae (V, VI and ventral horn) were labelled. 3 h after carrageenin administration, maximal Fos-like immunoreactivity was observed (104 labelled neurons per L4-L5 sections). At later time points Fos-like immunoreactivity was observed predominantly in the deeper laminae. Fos-like immunoreactivity was rarely observed within laminae III-IV at any of the time points. At 24 h, the number of Fos-like immunoreactive neurons decreased (36 labelled neurons per L4-L5 sections). With increasing doses of carrageenin, an increase in the number of Fos-like immunoreactive neurons was observed. The number of Fos-like immunoreactive neurons induced by the carrageenin stimulation (6 mg, at 3 h) was clearly reduced by oral pretreatment with indomethacin (20 mg/kg). In addition, i.v. indomethacin (1, 2.5 or 5 mg/kg) dose dependently reduced the number of Fos-like immunoreactive neurons and the inflammation of the paw and the ankle of the injected foot. A strong relationship between the effect of indomethacin on c-Fos expression and its effect on inflammatory processes was observed. These results suggest that Fos-like immunoreactivity induced by carrageenin inflammation may be a very useful tool to study the effects of anti-inflammatory drugs, at both peripheral and central levels of inflammation.