We examined the anxiolytic effects of a variety of anti-depressant drugs, administered either acutely or chronically, in an animal model of anxiety involving novelty-suppressed feeding in food-deprived rats. Following a single injection of desipramine (10 mg/kg), amitriptyline (10 mg/kg), mianserin (10 mg/kg), fluoxetine (10 mg/kg), buspirone (4 mg/kg), gepirone (4 mg/kg) or nomifensine (10 mg/kg), there was no decrease in the latency to begin eating in the novel environment such as occurred with diazepam (2 mg/kg). In fact, an increased latency was observed for desipramine, amitriptyline, fluoxetine, and nomifensine. In contrast, chronic (21 days) treatment with each of the above-mentioned drugs, except nomifensine, significantly reduced the latency to begin eating relative to vehicle controls. These findings suggest that a variety of tricyclic and novel anti-depressant drugs acquire anxiolytic properties following chronic administration.