Fructose has a reaction constant 7.5 times as high as that of glucose in its nonenzymatic reaction with protein in vitro. The effects of glucose, sucrose and fructose ingestion on serum fructose and glucose levels were studied to evaluate the overall biohazard, i.e., the probability of their altering proteins while circulating in the blood. Normal and diabetic subjects were given either 75 g glucose, 75 g fructose, 75 g sucrose, or 112.5 g fructose after fasting, and their serum levels of sugars were measured at 0, 1, 2 and 3 h. In normal subjects, fructose ingestion produced significantly lower serum glucose levels and significantly higher serum fructose levels than did glucose ingestion, while sucrose produced intermediate results. The glycemic effect was found to be lowest for fructose and highest for glucose. The calculated overall biohazard was, however, highest for fructose and lowest for glucose in normal subjects. Furthermore, the serum fructosemic index was directly proportional to the amount of fructose ingested. In diabetic subjects, blood fructose clearance was significantly more delayed than in the controls when the same amount of fructose was ingested. These results suggest that an evaluation of the effects of simple in the diabetic diet requires a closer examination of the overall biological effects of the sugars.