We examined the effects of dietary cholesterol on cardiac and hepatic beta-adrenergic receptor functioning. Age-matched adult desert rodents (Psammomys obesus) were randomized to either a 5% cholesterol diet (CD, n = 20), or normal rabbit chow (RC, n = 18). After a 2-month exposure to the diets, animals were sacrificed and tissue from both heart and liver were retained for radioligand bindings studies. In heart tissue, cholesterol fed animals, relative to controls, showed an increased production of adenosine 3,5>-cyclic monophosphate (cAMP) in response to isoproterenol. Cholesterol supplementation was not associated with an increase in heart beta-adrenergic receptor number. Animals fed the 5% cholesterol diet showed significant increases in the number of beta-adrenergic receptor sites in hepatic tissue (M = 13.2 vs. 10.4 pmol/mg protein, CD and RC, respectively). The increased number of receptor sites in the liver was accompanied by a significant increase in isoproterenol-stimulated cAMP production. Results are supportive of the hypothesis that dietary cholesterol contributes to an upregulation of beta-adrenergic receptor function in cardiac, as well as hepatic tissue. These findings may be relevant to the observations of excessive stress-induced cardiovascular reactivity in persons with high cholesterol levels.