Morphine (10 mg/kg), ethanol (8% w/v, 2 ml/kg), nicotine (0.1 mg/kg), cannabis extract (200 mg/kg), lorazepam (10 mg/kg) and ondansetron (0.1 mg/kg) were each administered to rats twice daily i.p. for 14 days and the anxiogenic response following their withdrawal was monitored by the elevated plus-maze test 24 h later. Brains were removed and endogenous monoamine oxidase (MAO) A and B inhibitory activity (tribulin) levels measured on day 14 and 24 h after drug withdrawal in different groups of animals. Morphine, ethanol, lorazepam and nicotine withdrawal was associated with significant anxiety and corresponding increase in brain tribulin activity, particularly its MAO A inhibitory component. Cannabis and ondansetron withdrawal were neither associated with anxiety or change in tribulin levels. The investigation supports the postulated role of tribulin as an endogenous correlate of anxiety, its MAO A inhibitory component accounting for a major part of this effect.