Transgenic mice expressing growth hormone genes have been shown to have kidney lesions resembling those found in human diabetic patients. However, transgenic mice expressing a growth hormone antagonist gene have normal kidneys. In this study, streptozotocin was used to induce diabetes in growth hormone or growth hormone antagonist transgenic mice and total glycated hemoglobin levels were determined. We found streptozotocin treatment resulted in a significant increase in glycated hemoglobin levels in these animals. Despite comparable levels of glycemia and glycated hemoglobin, severe glomerulosclerosis was found in diabetic and nondiabetic growth hormone transgenic mice; moderate glomerulosclerosis was seen in diabetic nontransgenic mice; and normal glomeruli were seen in diabetic and non-diabetic growth hormone antagonist transgenic mice as well as non-diabetic nontransgenic littermates. These results suggest that growth hormone is playing a role in diabetic nephropathy, and elevated levels of growth hormone can directly affect the kidneys independent of the levels of glucose and glycated hemoglobin.