Since growth hormone (GH) secretion is increased with fasting, the study was designed to assess the effects of short-term fasting on both basal and GH stimulated substrate metabolism. Seven normal healthy subjects were studied following a 12 h and a 36 h fast ("fasting"), for 2 h in the basal state and for a further 4 1/2 h after an i.v. bolus injection of 140 micrograms GH. As expected fasting induced decrements in circulating concentrations of insulin and C-peptide (p < 0.05) and increments in glucagon concentrations (p < 0.05), together with a slight increase in serum GH concentrations (p > 0.05). Furthermore plasma glucose values, isotopically determined turnover rate for glucose and forearm uptake of glucose were all substantially reduced during fasting (p < 0.05). By contrast circulating levels of all measured lipid intermediates (free fatty acids [FFA], 3-hydroxybutyrate [3-OHB] and glycerol) and the forearm uptake of 3-OHB were clearly elevated during the fast (p < 0.05). Serum GH rose to a peak of 17.0 +/- 2.7 within 10 min of injection in both situations. Blood concentrations of hormones and parameters of glucose metabolism remained unaffected. After administration of GH circulating levels of lipid intermediates increased markedly in both situations, the increase being most pronounced in the fasting state (p < 0.05). During fasting peak levels of 1775 +/- 150 mumol/l and 1780 +/- 360 mumol/l of FFA and 3-OHB were observed compared to postabsorptive peaks of 980 +/- 100 and 230 +/- 90 mumol/l respectively.(ABSTRACT TRUNCATED AT 250 WORDS)