We report an antagonistic interaction between tramadol and non-steroidal anti-inflammatory drugs (NSAIDs), on gastrointestinal transit in rats. Transit was evaluated with charcoal and results are expressed as %inhibition. Tramadol and morphine had ED(50)s of 120.70+/-9.54 and 3.20+/-0.26 mg/kg, respectively, while metamizol (85 mg/kg), paracetamol (100 mg/kg) or ibuprofen (50 mg/kg) had no effect. All combinations of tramadol plus an NSAID, resulted in a rightward, non-parallel shift of the curves, which showed (two-way analysis of variance, ANOVA) significant differences from tramadol alone for the dose (P<0.0001), the drug (P<0.0001) and their interaction (P<0.0001), demonstrating antagonism. No interaction was present for morphine plus NSAIDs. The results demonstrate that NSAIDs antagonise the constipating effects of tramadol in rats, a fact that could have clinical relevance when combinations of these drugs are used in pain management in humans.