The possession of intrinsic sympathomimetic activity (ISA) by a beta-adrenoceptor blocking drug results in a number of different pharmacologic properties. Most profound are the central hemodynamic effects. A drug with a significant degree of ISA results in less of a decrease in heart rate at rest and cardiac output, and, at least partly because of this, less of a decrease in peripheral blood flow. If prevailing sympathetic tone is low enough (e.g., during sleep) and the degree of ISA is sufficient, an increase in heart rate may be seen from an ISA-possessing drug. If the drug possesses beta 2 ISA, then a peripheral vasodilation action from stimulation of beta 2 vasodilator receptors may also be relevant. If high levels of exercise and full dosages of the drugs are used, a beta-blocking drug with ISA produces less of a decrease in heart rate. In asthmatic subjects, the modest beta-stimulant action on bronchial smooth muscle is not important, as these patients are potentially sensitive to any receptor blockade. Isoprenaline responses are inhibited to a similar degree compared with inhibition of exercise tachycardia, by nonselective drugs with and without ISA, whereas beta 1 selective agents produce much less inhibition of isoprenaline-induced tachycardia. A drug with ISA "down regulates" beta receptors; thus, when the drug is withdrawn there is no post-beta-blocking drug hypersensitivity in contrast to agents without ISA. There is evidence that ISA results in less of a disturbance in certain metabolic processes, particularly lipid metabolism and the metabolism of liver-metabolized drugs.