The beta-adrenergic receptor, its occupancy and subsequent modulation of intracellular cAMP, and mRNA expression were characterized for the promonocytic leukemia cell line THP-1. We report that THP-1 cells appear to express a beta-1 receptor with a Kd of 1.8 +/- 0.3 x 10(-11) microM and a B max of 108 +/- 0.07 fmole/mg protein using 125I-iodocyanopindolol (125I-ICYP). The potency of various beta-adrenergic agonists to compete for the 125I-ICYP binding site followed the order: isoproterenol (0.8 microM) > dobutamine (2.1 microM) > salbutamol (3 microM) > epinephrine (3.8 microM) > soterenol (4.6 microM) > terbutaline (11.1 microM) > norepinephrine (13.8 microM). Occupancy of the beta receptor on THP-1 cells results in activation of adenyl cyclase suggesting that these cells have a functional beta-adrenergic receptor. This receptor also has specific immunoregulatory properties, reducing message levels for tumor necrosis factor--but not interleukin 1, following treatment with isoproterenol (approximate EC-50 of 0.01 microM). We conclude, based on the above criteria, that THP-1 cells express a beta-1 receptor which, following ligand binding, results in increased cAMP leading to downregulation of TNF expression.