Respiratory depression is a common side effect when opioids are used to immobilize wildlife. Serotonergic ligands have the potential to reverse opioid-induced respiratory depression. We examined whether any of three serotonergic ligands could reverse this depression in etorphine-immobilized (0.07 mg/kg) impala (Aepyceros melampus). The study took place in September–December 2007. Impala received intravenous injections of metoclopramide (10 mg/ kg, n=6), buspirone (0.05 mg/kg, n=8), pimozide (1 mg/kg, n=8), doxapram (1 mg/kg, n=6), and control solutions on separate occasions. During the immobilization, partial pressures of oxygen (PaO2, mmHg) and carbon dioxide (PaCO2, mmHg), respiratory rate (breaths/min), ventilation (l/ min), peripheral O2 saturation (%), tidal volume (l), and respiratory exchange ratio were measured before and after injection of the experimental drugs. Etorphine immobilization caused respiratory depression and hypoxia (mean±SD, PaCO2=51±2 mmHg, PaO2=40±3 mmHg). Metoclopra-mide and buspirone, but not pimozide, attenuated the hypoxic effects of etorphine; 3 min after injection, metoclopramide increased the PaO2 by 7.=66.3 mmHg and buspirone by 666.6 mmHg (F=3.9, P=0.02). These effects were similar to those of doxapram (8±7 mmHg, F=3.9; P>0.05). Neither metoclopramide nor buspirone significantly increased ventilation, but they increased PaO2 by significantly improving the alveolar-arterial oxygen partial pressure gradient (A-a gradient, F=1.4, P<0.05), indicating improved oxygen diffusion. Metoclopramide and buspirone transiently improved blood oxygenation of opioid-immobilized impala, probably by improving ventilation-perfusion ratios, without reversing catatonic immobilization.