The effect of systemically administered oxytocin and a specific oxytocin antagonist, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin, on heat pain sensitivity was examined in rats. Intraperitoneal (i.p.) oxytocin at 1 mg/kg, but not at 0.1 and 0.3 mg/kg, significantly increased response latencies on the hot-plate test. However, the rats displayed clear signs of sedation, motor impairment and vasoconstriction after 1 mg/kg oxytocin. Skin temperature on the plantar surface of the hind paws was also significantly decreased by this dose of oxytocin. The oxytocin antagonist (1 mg/kg i.p.) did not influence response latency. Since increased response latency was not the only behavioral effect of oxytocin, we conducted electrophysiological experiments to examine the effect of systemic oxytocin on the nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats. Oxytocin at 0.1 mg/kg i.p. did not influence flexor reflex magnitude, mean blood pressure or heart rate. Oxytocin at 0.3 and 1 mg/kg caused a gradual increase in blood pressure with stronger effect observed with 1 mg/kg. Neither 0.3 nor 1 mg/kg oxytocin significantly influenced the flexor reflex magnitude and heart rate. We thus conclude that systemic oxytocin did not produce analgesia in rats and the observed increase in response latency in the hot-plate test may result from the sedative and vasoconstrictive effects of this peptide. Furthermore, since the oxytocin antagonist did not significantly alter response latency on the hot-plate test, it is unlikely that endogenous oxytocin exerts a tonic effect on the pain threshold in rats.