1 The availability of the non-peptide 6-opioid receptor antagonist naltrindole has provided the possibility for in vivo studies on the function of 6-opioid receptors. We have studied the effects of naltrindole on swim-stress-induced antinociception in adult and neonatal rats. 2 Adult, 25 and 20 day old rats were stressed by warm water (20°C) swimming for 3min periods and antinociception was assessed by the tail immersion test (50°C). 3 Naltrindole (0.5 and 1 mgkg 1) antagonized swim-stress-induced antinociception in adult and 25 day old rats but in 20 day old rats naltrindole (1 mg kg-1) was without effect. 4 Antinociception induced by the highly p-opioid receptor selective agonist alfentanil was completely antagonized by naloxone (1 mg kg-1) but virtually unaffected by naltrindole (1 mg kg-'). 5 Neither naloxone nor naltrindole (1 mg kg-1) antagonized swim-stress-induced rises in plasma corticosterone in adult rats at the time of peak antinociception. 6 In conclusion, naltrindole shows in vivo antagonism of opioid-mediated responses. Swim-stressinduced antinociception is mediated through the b-opioid receptor in 25 day old and adult rats and through the p-opioid site in 20 day old animals.