Gamma-hydroxybutyric acid has been proposed as a pharmacotherapy for alcoholism in part based on similar discriminative stimulus effects as ethanol. To date, drug discrimination studies with γ-hydroxybutyric acid and ethanol have exclusively used rodents or pigeons as subjects. To evaluate possible differences between species, sex, and route of administration, this study investigated the substitution of γ-hydroxybutyric acid (intragastrically or intramuscularly) for ethanol 30 or 60 min after administration in male (n=6) and female (n=7) cynomolgus monkeys trained to discriminate 1.0 and 2.0 g/kg ethanol. At least one dose of γ-hydroxybutyric acid completely or partially substituted for ethanol in three of the 13 monkeys tested, with each case occurring in female monkeys. Ethanol-appropriate responding did not increase with γ-hydroxybutyric acid dose. Monkeys were more sensitive to the response rate decreasing effects of γ-hydroxybutyric acid administered intramuscularly compared with intragastrically. The lack of γ-hydroxybutyric acid substitution for ethanol suggests that these drugs have different receptor bases for discrimination. Furthermore, the data do not strongly support shared discriminative stimulus effects as the rationale for γ-hydroxybutyric acid pharmacotherapy for alcoholism.