Insulin 0.05 mu/kg body weight was injected intravenously into 14 subjects both at 8 a.m. and 5 p.m. in random order 12 hrs after a 50 g glucose meal. Fasting glucose levels were similar in both cases but the 48percent plus or minus 10 percent fall in blood glucose in the morning was significantly greater (p smaller than 0.001) than that of 34 percent plus or minus 7 percent in the afternoon. Fasting plasma NEFA, however, varied markedly between 477 plus or minus 150 muEqlL in tth morning and 725 plus or minus 195 muEqlL in the afternoon (p smaller than 0.001) and the fall after insulin injection (64 percent plus or minus 14 percent) was greater in the afternoon than in the morning (47 percent plus or minus 15 percent) (p smaller than 0.001). There was an inverse relationship between proportional glucose disappearance and proportional NEFA disappearance (p smaller than 0.001). The calculated caloric change in plasma, the sum of the falls in glucose and NEFA, were very similar in both morning (2.2 plus or minus 0.5 Cals/1) and afternoon (2.3 plus or minus 0.5 Cals/1), i.e., in spite of the variations of glucose and NEFA metabolism produced by insulin at different times, the nett effect, in terms of energy, was the same. Plasma growth hormone response in the afternoon was found to be enhanced compared with the morning values, although the degree of hypoglycaemia was greater in the morning.