Incubation of human immunoglobulin G (IgG) with glucose in vitro leads to the formation of glycated IgG concomitant with marked changes in functional properties of the Fc fragment. After 22 days of incubation in the absence and presence of 13.9, 27.7 and 55.5 mmol/l glucose, respectively, protein A binding was reduced by 42, 66 and 83%, depending on the glucose concentration employed. Binding of complement by IgG was abolished after incubation of the immunoglobulins for 13 days at 13.9 mmol/l glucose. In contrast, functional properties of the Fab region were unaffected upon glycation, as revealed by determination of antigen-binding capacity, antibody affinity and antibody concentration. The functional changes of the Fc fragment were observed at glycation levels comparable to those found in diabetics.