Diabetes and aging are associated with an increase in collagen-linked fluorescence and cross-linking that can be duplicated by incubating collagen with glucose. We have tested the hypothesis that browning and cross-linking can occur in vivo in rats by feeding them a diet containing 33% galactose. No significant increase in tail tendon browning or cross-linking, measured by tail tendon breaking time in urea, was observed after 3 mo of galactosemia. After 12 mo, however, twofold increases in tendon breaking time and collagen-linked chromophores absorbing greater than 300 nm and fluorophores at 430 nm (excitation 355 nm, P less than .001) analogous to those of diabetic and aging individuals were observed. The observed changes in collagen are attributed to the advanced Maillard (nonenzymatic glycosylation) reaction based on circumstantial evidence. With this premise, our data suggest that chronic galactosemia should be a powerful tool for investigating the role of the advanced Maillard reaction in complications of diabetes and aging.