Norepinephrine, epinephrine, and histamine cause a rapid increase in the concentration of adenosine 3':5'-cyclic monophosphate (cAMP) in a tumor astrocyte cell line derived from a primary culture of a human glioblastoma multiforme. The catecholamine-induced increase in cAMP is dependent on the cell density, being far greater in cells in the log phase of growth than in cells near terminal density. The response to norepinephrine is inhibited 50% by 0.01 muM propranolol, a blocking agent of beta-adrenergic receptors. In contrast, the effect of histamine on cAMP concentration varies only slightly from log-phase growth to terminal density, and is not inhibited by 10 muM propranolol. The results suggest that astrocytoma cells have independent receptors for catecholamines and histamine. Further, if the astrocytoma cell is an adequate model of the normal glial cell, these results suggest that astrocytes in human cerebral cortex may be sensitive to norepinephrine and histamine.