Forced swimming stress-induced antinociception (FSSIA) was assessed using the formalin test. Male ICR mice, weighing about 30 g, were forced to swim in water at 20 degrees C for 3 min. In unstressed mice, SC injection of formalin (0.5%) to the hindpaw caused a biphasic response: an immediate nociceptive response (first phase) followed by a tonic response (second phase). Although forced swimming stress (FSS) had no effect on the duration of the first-phase response, FSS significantly reduced the duration of the second-phase response. The effect of FSSIA on the second-phase response was blocked by naltrindole (1 mg/kg, SC), a selective delta-opioid receptor antagonist, but not by beta-funaltrexamine (20 mg/kg, SC), a selective mu-opioid receptor antagonist. These results indicate that FSS may selectively reduce the second phase of the formalin-induced nociceptive response, primarily through delta-opioid receptors.