An increase of basement membrane thickness in renal glomeruli, blood vessels, and other tissues is a consistent pathological observation in individuals with diabetes mellitus. Although a number of pathological complications of the disease are thought to result from this structural abnormality in basement membranes, the mechanism(s) responsible for this glucose-mediated process remain unknown. The current study was designed to develop a non-mammalian in vivo epithelial/basement membrane model which would facilitate detailed analysis of the cellular and molecular processes which lead to thickening of basement membrane under hyperglycaemic conditions. The system developed utilizes the Cnidarian, Hydra vulgaris. Hydra lends itself to such studies because of (1) its simplified body structure which is composed of an epithelial bilayer with an intervening basement membrane (mesoglea) and (2) its extensive regenerative capacity which allows cell pellets (Hydra cell aggregates), formed from isolated Hydra cells, to develop into adult Hydra within 72-96 h. This process involves reformation of an epithelial bilayer and de novo biosynthesis of a basement membrane. Our studies indicate that exposure of developing Hydra cell aggregates to levels of D-glucose which mimic that observed in the human diabetic patient (15 mmol/l) induces a doubling of Hydra basement membrane thickness within 72-96 h of pellet formation. The same results were obtained using 15 mmol/l D-Ribose which is a highly efficient glycating agent. The data presented support the use of the Hydra cell aggregate system as a potentially powerful non-mammalian in vivo model to investigate the cellular and molecular mechanism(s) underlying glucose-mediated basement membrane thickening.