The influence of extracellular and intracellular angiotensin II (Ang II) on the cell volume in the failing heart of cardiomyopathic hamsters (TO2) was further investigated as well as the influence of aldosterone and spironolactone on the Ang II action on cell volume. Measurements of cell width and area of quiescent ventricular cardiomyocytes were performed using a video camera and computer analysis and the relative cell volume was calculated. All measurements of cell volume were performed in the same cell before and after the administration of Ang II (10⁻⁸M). The results indicated that: a) the increase in cell volume caused by extracellular Ang II(10⁻⁸ M) was enhanced in cells incubated with aldosterone (100 nM) for 48 h; b) the effect of aldosterone was abolished by spironolactone (10⁻⁸ M); c) the decline in cell volume elicited by intracellular administration of Ang II (10⁻⁸ M) was increased by aldosterone and inhibited by spironolactone; d) the effects of aldosterone and spironolactone were related, in part, to a change in expression of AT1 receptors; and e) the intracellular administration of Ang II reduced the swelling-dependent chloride current (I(Clswell)). The implications of these findings to the failing heart and myocardial ischemia are discussed.