Abstract The purpose of the present study was to investigate the possible regulation of plasma fatty acids by an acute isotonic-isooncotic central volume expansion. We measured the levels of nonesterified fatty acids (NEFA) in plasma from 12 essential hypertensive patients subjected to water immersion (WI). Central hypervolemia by WI over 2 hours caused the levels of most NEFA to increase, concomitantly with a marked natriuretic and kaliuretic response. With respect to baseline values, serum insulin levels did not change during WI, while there was a profound suppression of plasma renin activity (PRA) and plasma aldosterone. In addition, when individual NEFA percent increase was expressed as a function of salt-sensitivity index (calculated as the change in mean arterial pressure [MAP] divided by the change in urinary sodium excretion rate), a greater percent increase in stearic acid (r =.72, P <.009), palmitic acid (r =.83, P <.001), and palmitoleic acid (r =.58, P <.048) was found during WI in those hypertensive subjects showing higher salt-sensitivity index. Thus, by demonstrating that an acute isotonic-isooncotic volume expansion may induce a significant increase of most NEFA plasma levels, we suggest that volume expansion per se could be included among the well-recognized risk factors for cardiovascular morbid events. Copyright 2003 Elsevier, Inc. All rights reserved.