Beta-adrenoceptor desensitization (loss of response) and down-regulation (loss of receptors) are a consequence of an increased activity of the sympathetic nervous system in the failing human heart. In some heart diseases β1adrenoceptors are selectively decreased, whereas others seem to be characterized by a reduction of both β1and β2subtypes. Changes in messenger RNA levels for the β1sybtype and the β-adrenoceptor kinase, an enzyme that phosphorylates β adrenoceptors resulting in receptor uncoupling, appear to be significant in the desensitization and down-regulation in the failing heart. Angiotensin-converting enzyme inhibitors have beneficial effects in the therapy of heart failure. Beta-adrenoceptor antagonists are potentially another class of agents that could improve cardiac function.