The rate of nonenzymatic glycosylation of serum albumin was determined in 7 diabetic patients at the onset and during the recovery of an acute metabolic derangement as defined by hyperglycemia, hyperosmolality and metabolic acidosis of various degrees. Serum glycosyl albumin concentration (chemically determined) was decreased after 1 day in 5 patients (mean -6%) and increased in the remaining 2 (+11% and +22% respectively). The same variance was decreased in the whole group after 7 days of therapy (-18.6%). A negative statistical correlation was found by plotting initial values of serum glycosyl albumin against arterial H+ concentration and the same relationship was confirmed by multiple regression analysis which gave the following curve: t (glycosyl albumin) = 1.57 - 0.004 X (H+) + 0.000225 y (Mean blood glucose concentration) - 0.00285 z (serum osmolality) (the regression coefficients were 0.24 for x, 0.18 for y and 0.23 for z). Finally, a number of albumin isoforms with a cationic charge up to 7 pH have been detected in all patients by isoelectric focusing. Taken together all the data presented herein indicate that beside serum glucose concentration other factors (such as H+ concentration and serum osmolality) influence the rate of glycosylation of albumin, their effects being prominent and opposite to hyperglycemia.