We have previously reported that repetitive, noxious colorectal distention (CRD) induces c-Fos in the lumbosacral spinal cord. This study examined the effects of the analgesics morphine and tramadol on c-Fos expression resulting from noxious CRD in the rat. Pre-treatment (30 min or 1 min, i.v.) with morphine (1.25 mg/kg-5.0 mg/kg) or tramadol (1 mg/kg-20 mg/kg) dose-dependently attenuated c-Fos expression to CRD in all areas of the L6-S1 spinal gray matter. The highest dose of morphine was equipotent to the highest dose of tramadol. Repetitive dosing (1/4 of the greatest dose every 30 min) was as effective as a single bolus dose for both drugs. The visceromotor response to CRD was dose-dependently attenuated by tramadol and was reversed by naloxone. However, the dose of tramadol that eliminated the visceromotor response (7% of control) reduced the c-Fos expression to 47% of control. These results demonstrate that these two analgesics attenuate immediate-early gene expression and the visceromotor response to a noxious visceral stimulus and suggest that complete attenuation of c-Fos expression is not necessary for these compounds to produce analgesia to a noxious visceral stimulus.