A long-acting analgesic is particularly desirable in patients with long-lasting pain. In this study, we evaluated the antinociceptive effect and duration of action of three nalbuphine esters-nalbuphine propionate, enanthate, and decanoate-and observed whether these esters had a long-acting effect. Male Sprague-Dawley rats (n = 12 in each group) were used. Two studies were performed. In Study 1, we evaluated the antinociceptive effect of IM nalbuphine HCl with dosages of 0.25, 1.25, 2.5, 25, and 250 micro mol/kg. In Study 2, we evaluated the antinociceptive effects of IM nalbuphine base and esters with a dosage of 25 micro mol/kg. After 2.5, 25, and 250 micro mol/kg IM injections, we found that nalbuphine HCl produced a dose-related antinociceptive effect with durations of action of 1.5, 2, and 4 h, respectively. After a 25 micro mol/kg IM injection, the durations of action of the nalbuphine esters, nalbuphine propionate, enanthate, and decanoate were 5, 30, and 60 h, respectively. We conclude that, on an equimolar basis, nalbuphine esters produce relatively longer durations of action than nalbuphine HCl.