During the past decade a number of investigators have attempted to develop mouse models of diabetic macrovascular disease. Hyperglycemia might increase vascular damage because it increases oxidant stress. For this reason we studied animals that were deficient in HDL; HDL is widely believed to protect against oxidant stress. An inbred line of mice doubly deficient in LDL receptor and apoAI was made diabetic with streptozotocin (STZ); control mice had an average glucose of 7.2+/-2mmol/l and STZ-treated mice had an average glucose of 19.4+/-6.5mmol/l. The animals were fed a high cholesterol but low fat diet leading to plasma cholesterol levels of 9.4+/-1.6mmol/l in control animals and 10.1+/-1.8mmol/l in STZ-treated mice. The control and STZ-treated animals had similar plasma lipoprotein profiles. Atherosclerosis assessed at 23 weeks averaged 38154microm(2) in control and 32962microm(2) in STZ-treated mice. Therefore STZ-induced diabetes does not alter plasma lipoproteins or atherosclerosis in HDL deficient mice.