In 44 diabetic patients treated either with insulin or with oral antidiabetic agents, non-enzymatic glycosylation of serum proteins (GSP), expressed as nmol of 5-hydroxymethylfurfural/mg protein, showed higher values than those found in control subjects. In the diabetic GSP was more closely correlated to the degree of glycometabolic control during the 15 days preceding the assay, than to the glycosylated hemoglobin (HbA1). However, GSP values did not correlate significantly with fasting blood glucose levels. It may be concluded that GSP can be used as an index of the medium-term control of diabetes mellitus.