Desipramine (DMI, 15 mg/kg, s.c.) decreased [3H]CGP-12177-labelled cortical beta-adrenoceptor density (Bmax) by 30% upon chronic (14 day) treatment. However, even a single dose (in mg/kg) of DMI (15) or the beta-adrenoceptor agonist, clenbuterol (20), induced a rapid (24 hour) and significant reduction of beta-adrenoceptor Bmax (-15%; p < 0.01). Acute treatment with amitryptiline (10), clorgyline (1), fluoxetine (10), nomifensine (10) or maprotiline (20) had no significant effect on [3H]CGP-12177-labelled beta-adrenoceptors, suggesting that rapid down-regulation may not be a general property of antidepressant drugs. None of the antidepressants altered the Bmax of [3H]ketanserin-labelled 5-HT2A receptors on acute treatment. These results show that beta-adrenoceptor down-regulation by clenbuterol and DMI is not dependent on chronic treatment and may, therefore, be a poor correlate of the gradual onset of therapeutic efficacy seen clinically with antidepressant drugs.