Hyperglycemia associated with the manifestation of the obese diabetic (ob/ob) syndrome in mice and the short and long term streptozotocin treatment of lean MF1 mice was accompanied by a significant decrease in erythrocyte glyoxalase 1 activity and a marked increase in the concentration of the alpha-oxoaldehyde methylglyoxal. Erythrocyte glyoxalase II activity was modestly but significantly elevated in both obese mice and short term streptozotocin treated MF1 mice but no significant changes in S-D-lactoylglutathione concentration could be detected. Modification of the cells glyoxalase system during hyperglycaemia, especially the enhanced production of methylglyoxal may be a significant biochemical factor in the development of diabetic complications.