Background: In patients undergoing colonoscopy, naloxone has vasodilative properties. However, it remains unclear whether this effect is mediated by central or peripheral mechanisms. The aim of this study was to investigate whether these effects are mediated by an effect of naloxone on the central nervous system. Methods: Twenty dogs were chronically instrumented for measurement of hemodynamic parameters. Splanchnic blood flow was determined using colored microspheres. Transthoracic echocardiographic examinations were performed to measure cardiac output. In each animal, two experiments were performed in a random order: experiment 1 was determination of splanchnic blood flow before and 5 min after intravenous administration of naloxone (63 mug/kg), and experiment 2 was determination of splanchnic blood flow before and 5 min after administration of naloxone methiodide (63 mug/kg), which does not cross the blood-brain barrier. Results: Naloxone, but not naloxone methiodide, significantly increased blood flow to the stomach (from 0.41 +/- 0.022 to 0.9 +/- 0.016# ml.g(-1).min(-1) with naloxone), jejunum (from 0.31 +/- 0.024 to 0.83 +/- 0.083# ml.g(-1).min(-1) with naloxone), colon (from 0.41 +/- 0.057 to 0.68 +/- 0.008# ml.g(-1).min(-1) with naloxone), spleen (from 1.45 +/- 0.21 to 2.13 +/- 0.25# ml.g(-1).min(-1) with naloxone), pancreas (from 0.97 +/- 0.021 to 1.25 +/- 0.005# ml.g(-1).min(-1) with naloxone), and kidneys (from 3.24 +/- 0.108 to 5.31 +/- 0.26# ml.g(-1).min(-1) with naloxone), without, altering cardiac output or arterial blood pressure in conscious dogs. There were no differences in the hemodynamics or cardiac output between the two experiments. Data are presented as mean +/- SD. Conclusions: The increased splanchnic perfusion after naloxone is not caused by direct peripheral vascular effects or increased cardiac output. Indirect vasodilative effects on splanchnic vessels mediated by actions of naloxone on the central nervous system account for the increased gastrointestinal perfusion after naloxone in dogs.