Previous studies have demonstrated an upregulation of interleukin-1 (IL-1) receptors following treatment of mouse AtT-20 pituitary tumor cells with corticotropin-releasing factor (CRF). In the present study, we determined the modulation of IL-1 receptors and adenylate cyclase activity in AtT-20 cultures following treatment with CRF, isoproterenol, forskolin, somatostatin and dexamethasone. CRF, isoproterenol and forskolin dose-dependently increased cAMP production and [I-125]IL-1 alpha binding. In contrast, somatostatin and dexamethasone significantly inhibited CRF-stimulated cAMP production and decreased both basal and CRF-mediated increases in [I-125]IL-1 alpha binding. Parallel modulation of IL-1 receptors by agents that stimulate (CRF, isoproterenol and forskolin) or inhibit (somatostatin) cAMP production in AtT-20 cells suggest the importance of this second messenger in regulating IL-1 receptors.