Background: GABAergic drugs can modulate the rewarding properties of morphine. The objective of this study was to evaluate the effects of isoniazid, as a GABAergic agent, on the rewarding effects of morphine. Methods: Eighteen groups of female mice (eight per group) were used in a conditioned place preference (CPP) study. On the conditioning phase of the CPP procedure, ten groups of the animals received morphine (0, 0. 75, 1. 5, 3, 5, and 10 mg/kg, s. c. ) or isoniazid (0, 25, 50, and 75 mg/kg, i. p. ) to induce CPP. Then, the effects of isoniazid on the acquisition and expression of morphine-induced CPP were evaluated. In the expression experiment, four groups of mice were conditioned with an effective dose of morphine (5mg/kg, s. c. ). Then, the animals received saline or isoniazid (25, 50, and 75 mg/kg) one hour before the test, intraperitoneally. In the acquisition experiment, the other four groups received intraperitoneal saline or isoniazid (25, 50, and 75 mg/kg, i. p. ) one hour before receiving the effective dose of morphine (5mg/kg, s. c. ) on conditioning phase. On the test day, these animals received no treatment. Results: Morphine but not isoniazid induced a significant CPP in mice. Morphine or isoniazid alone did not change the locomotor activity of the animals on the test day. Isoniazid pretreatment could significantly inhibit both the acquisition and expression of the morphine-induced CPP. Isoniazid also did not influence the locomotor activity of the animals in the expression and acquisition experiments. Conclusion: Isoniazid may have a therapeutic application in morphine addiction.