Quantitative receptor autoradiography was used to study the effects of the selective serotonin reuptake inhibitors citalopram and fluoxetine and the tricyclic antidepressant imipramine on the regulation of beta 1-adrenergic receptors in the rat brain. Rats were treated with saline, citalopram (10 mg kg-1), fluoxetine (10 mg kg-1), or imipramine (15 mg kg-1) SC once daily for 14 days. [125I]Iodocyanopindolol binding to beta 1-adrenergic receptors was found to increase significantly in the caudate-putamen and the somatosensory areas of the frontal cortex after both citalopram and fluoxetine treatments. Imipramine treatment elicited a marked decrease in beta 1 binding in the outer laminae of the cingulate cortex, as well as in the motor and somatosensory areas of the frontal cortex. In a separate experiment, rats were treated with saline, citalopram (2.5, 10 and 20 mg kg-1) or fluoxetine (2.5, 10 and 20 mg kg-1) SC once daily for 14 days. The effects of citalopram and fluoxetine on beta 1 receptors in the somatosensory cortex and caudate-putamen were replicated. These results demonstrate that chronic administration of selective serotonin reuptake inhibitors, in contrast to imipramine, can cause a regional up-regulation of beta 1-adrenergic receptors in the rat brain.