Nonenzymatic glycosylation of albumin was associated with an increased catabolic rate and decreased protein half-life in both normal and diabetic animals. The fractional catabolic rate of glycosylated albumin was increased significantly over albumin, from 0.100 +/- 0.004/day to 0.131 +/- 0.007/day in normal animals and from 0.104 +/- 0.004/day to 0.138 +/- 0.007/day when these animals were made diabetic with alloxan. The half-lives of Alb and GlyAlb in normal dogs were 6.81 +/- 0.12 days and 4.97 +/- 0.21 days, respectively. In diabetic animals, the half-lives of Alb and GlyAlb were 7.48 +/- 0.21 and 5.21 +/- 0.24 days, respectively. The increased catabolism of GlyAlb may reflect chronic increased extravasation of glycosylated plasma proteins, which are known to be increased in diabetes, into the microvascular wall.