Insulin and glucose are thought to act as important modulators of the expression of the IGFs, their binding proteins and their receptors. It has been postulated that changes of the IGF system after diabetes onset contribute to the development of diabetes late complications. We have measured the expression of IGF-II/M6P receptor mRNA in rat kidney, lung and heart after streptozotocin induction of diabetes. Adult rats were injected with streptozotocin, and, after the onset of diabetes, were treated with either insulin or vehicle. The rats were sacrificed on days 1, 2, 3, 4 and 9. Kidneys, lungs and hearts were removed aseptically and RNA was extracted from the tissues. In solution hybridization/RNAse protection experiments, specific IGF-II/M6P receptor and beta-actin transcripts were detected in the RNA samples from all tissues examined. To gain additional evidence for the expression of IGF-II/M6P receptor RNA in the tissues examined, Northern blotting experiments were performed: a major 9 kb RNA species was detected on the blots. Interestingly, streptozotocin-induced onset of diabetes led to a significant increase in the expression of IGF-II/M6P receptor mRNA in the kidney but not in lung and heart whereas no change in actin mRNA expression was measured. Insulin treatment did not prevent the increase of IGF-II/M6P receptor mRNA expression during short-term treatment (1-9 days). Alterations of the IGF system during diabetes onset might be of relevance for the development of early renal changes during the course of the disease.