The effects of daily administration to rats of desipramine, talsupram, tomoxetine, maprotiline, nomifensine, mianserin and citalopram (each 10 mg kg-1 day-1) for 4 weeks on [3H]dihydroalprenolol ([3H]DHA) binding in the cerebral cortex and on the noradrenaline-sensitive adenylate cyclase in the limbic forebrain were determined. Of these compounds, desipramine was alone in reducing [3H]DHA binding and in attenuating the cAMP response. Two selective noradrenaline uptake inhibitors, talsupram and tomoxetine each reduced the cAMP response but without affecting [3H]DHA binding. The other drugs lacked effect on both measures indicating (except for citalopram) that reduction in sensitivity of beta-adrenoceptors and of the noradrenaline-sensitive cAMP response might not be a simple consequence of noradrenaline uptake inhibition. The lack of effect of citalopram on the sensitivity of the beta-adrenoceptor system suggests that antidepressants with selective 5-HT uptake inhibitory properties owe their antidepressant activity to other mechanisms.