The mechanism of the analgesic activity of paracetamol (acetaminophen), one of the most widely used drugs for the treatment of pain, is still not clear. Here we show that in rats, using the hot plate test, the analgesic effect of paracetamol is prevented by two antagonists at cannabinoid CB 1 receptors (AM281 and SR141716A) at doses that prevent the analgesic activity of the cannabinoid CB 1 agonist HU210. Our present results suggest that paracetamol-induced antinociception involves the cannabinoid system.