Hexacarbon compounds are neurotoxic to man and animals. These substances also inhibit various enzymes in vitro, including acetylcholinesterase. Since some cholinesterase inhibitors alter nociception we determined the effect of acute ip administration of 2,5-hexanedione on nociception in female Wistar rats (75-90 days old, 170-200 g; 15-17 rats in each group) using a tail-flick apparatus. The rats were injected ip with vehicle solution (120 mM NaCl containing 10 mM potassium phosphate buffer, pH 7.2) and 200, 400 or 800 mg/kg of 2,5-hexanedione in a volume of 1 ml/kg body weight. Tail-flick latencies were obtained 10, 30, 60 and 90 min after drug administration. All doses of 2,5-hexanedione caused antinociception (P less than 0.001) but the appearance and duration of the analgesia varied according to the dose of the drug. The highest dose tested (800 mg/kg) caused analgesia from 10 to 60 min, 400 mg/kg caused analgesia at 30 and 60 min, and 200 mg/kg produced antinociception only at 60 min after drug injection (P less than 0.05 for all the above comparisons). These results suggest that 2,5-hexanedione induces antinociception in rats. Whether this effect is mediated by a cholinergic mechanism is under investigation.