Blood lipids may detrimentally affect autonomic and circulatory control. We tested the hypotheses that acute elevations in free fatty acids and triglycerides (acute hyperlipidemia) impair baroreflex control of cardiac period [cardiovagal baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA: sympathetic BRS), increases MSNA at rest, and augments physiological responses to exercise. Eighteen young adults were examined in this randomized, double-blinded, and placebo-controlled study. BRS was determined using the modified Oxford technique before (Pre) and 60-min (Post) after initiating infusion of Intralipid (0.8 ml/m²/min) and heparin (1000 Units/hr) (experimental; n=12), to induce acute hyperlipidemia, or saline (0.8 ml/m²/min) and heparin (1000 Units/hr) (control; n=6). Responses to isometric handgrip to fatigue (IHG) were also determined. Blood pressure increased more (P0.05) in experimental than control subjects during the infusion. MSNA at rest (14±2 vs. 11±1 bursts/min), cardiovagal (19.8±1.8 vs. 19.1±2.4 ms/mmHg Pre and Post, respectively) and sympathetic BRS (-5.5±0.6 vs. -5.2±0.4 au/beat/mmHg), and the neural and cardiovascular responses to IHG were unchanged by acute hyperlipidemia (Pre vs. Post) in experimental subjects. Similarly MSNA at rest (10±2 vs. 12±2 bursts/min), cardiovagal (22.1±4.0 vs. 21.0±4.6 ms/mmHg) and sympathetic BRS (-5.8±0.5 vs. -5.5±0.5 au/beat/mmHg), and the neural and cardiovascular responses to IHG were unchanged by the infusion in control subjects. These data do not provide experimental support for the concept that acute hyperlipidemia impairs reflex cardiovagal or sympathetic regulation in humans.