Twenty-four military cadets went through a 5-day period of heavy physical exercise (35% of max O2 uptake), severe calorie supply deficiency (about 36,000 kJ/24 h), and sleep deprivation (2 h of sleep as a total during 5 days). Some cadets compensated for the caloric deficiency, whereas others partly compensated for the sleep deprivation. Fasting and meal- and glucose-induced changes in the plasma concentration of vasoactive intestinal polypeptide (VIP) were measured on separate days during the course and 8 h after the course was finished (day 6). Fasting plasma concentration of VIP increased two- to five-fold during the course, with the highest increase on day 2. The calorie-compensated subjects showed a smaller increase than those who did not receive any calorie or sleep compensation. Intake of a meal or glucose solution lowered the VIP concentration in plasma within 30-60 min to the concentrations found in the control experiments performed several weeks after the course. The results indicate a role of VIP as 'a polypeptide of substrate need'.