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Blood pressure, as well as blood volume homeostasis, depends to a large extent on humoral influences stemming from the renin–angiotensin axis and the sympathetic nervous system. Evidence has been provided that a large part of this homeostatic modulation is effected by the complex interactions between the two systems.The present review will focus on three major issues. First it will examine the physiological and pathophysiological relevance of angiotensin–sympathetic crosstalk discussing possible sites, mechanisms and effects of the interaction. It will then address the clinical relevance of these inter-relationships by reviewing data collected in cardiovascular and non-cardiovascular diseases. Finally, the influences of angiotensin II on adrenergic function will be examined as possible targets of cardiovascular drug treatment.By interrupting the influences of angiotensin II on sympathetic function, therapeutic interventions aimed at blocking the renin–angiotensin system exert favourable effects on the haemodynamic, metabolic and renal profile. This has important implications for the treatment of hypertension, congestive heart failure, renal insufficiency and metabolic syndrome.