The effect of fasting for 12, 36 and 72 h was studied in twenty-nine healthy subjects (seventeen women and twelve men). Measurements were made of cardiovascular variables, metabolic rate, respiratory exchange ratio, plasma metabolites, insulin, thyroid hormones and catecholamines. During starvation there were no significant changes in blood pressure, whilst heart rate (beats/min) increased at 36 h and remained elevated after 72 h (12 h 62.5 (SE 1.8), 36 h 68.0 (SE 1.9), 72 h 69.2 (SE 1.8); P < 0.001). Forearm blood flow (FBF) increased progressively from 3.32 (SE 0.20) to 6.21 (SE 0.46) ml/100 ml per min (P < 0.001). Resting metabolic rate (kJ/min) was significantly increased after 36 h of starvation (12 h 4.60 (SE 0.14), 36 h 4.88 (SE 0.13), P < 0.001), but was not significantly different from the 12 h value after 72 h (72 h 4.72 (SE 0.15) P = 0.06). The respiratory exchange ratio fell progressively from 0.80 to 0.76 to 0.72 (P < 0.001). Blood glucose fell, whilst plasma glycerol and beta-hydroxybutyrate rose and plasma lactate did not change. Plasma insulin and free triiodothyronine fell during starvation. Plasma adrenaline and noradrenaline were unchanged at 36 h, but were significantly increased after 72 h. Both sexes showed a similar pattern of response to starvation, although absolute values of blood pressure, forearm blood flow, metabolic rate and plasma catecholamines were higher in men than women. Acute starvation produces profound cardiovascular and metabolic changes which are not explained by the accompanying hormonal changes.