To assess the influence of fasting on the lipolytic effect of catecholamines in vivo noradrenaline (NA) was infused to 15 obese subjects before and after 7 days of fasting. The infusion of 7.5 microgram/min NA for 10 min was associated with a greater lipolytic response during than before fasting, as judged from changes in the plasma FFA and glycerol levels. The hemodynamic effects of NA were similar in both conditions. NA sensitivity was tested by infusing the hormone at an increasing rate from 0.05-2 microgram/min. During fasting, there was a 10-fold increase in the sensitivity to the lipolytic effect of NA, and the NA infusion significantly reduced the mean serum insulin level. Before fasting, the insulin level was constant during NA infusion. The increments in the plasma NA concentration were similar in both conditions. When insulin was infused at a constant rate, and graded NA doses were infused simultaneously, no lipolytic effect of NA at rates of 1 and 2 microgram/min significantly increased the plasma glycerol level. Thus, fasting enhances the lipolytic effect of NA in vivo, and this effect is due to increased sensitivity to NA and also to NA-induced depression of the circulating insulin level.