It was the purpose of the present study to assess the hemodynamic effects of adrenergic beta-receptor blocking drugs possessing intrinsic sympathomimetic activity (ISA) and/or beta 1 selectivity, both at rest and during exercise. The hemodynamic effects of seven different beta-blockers (propranolol, atenolol, acebutolol, ICI 72,222, ICI 89,406, and pindolol) were studied at rest in patients with ischemic heart disease. Heart rate (HR), cardiac output (CO), arterial blood pressure (BP), and pulmonary artery pressure (PP) were determined. At rest, it was possible to subdivide the various beta-blockers into three main groups according to the degree of ISA. One group without ISA, including propranolol and atenolol, reduced CO by 25% and HR by 15%. A second group with moderate ISA, represented by practolol, acebutolol and ICI 72,222, reduced CO only by 15% and HR by 10%. A third group with pronounced ISA, represented by pindolol and ICI 89,406, did not change CO and HR significantly. All three groups consisted of drugs both with and without beta 1 selectivity. During exercise, pindolol and propranolol reduced CO, HR, and BP to the same extent. In conclusion, the central hemodynamic response to beta-blockers at rest is determined by the degree of ISA, whereas beta 1 selectivity does not modify the central hemodynamic response to beta-blockade. However, the hemodynamic differences between adrenergic beta-blocking drugs with and without ISA disappear in situations with increased sympathetic drive, such as exercise.