Elevated levels of immunoreactive hypothalamic neuropeptide Y have recently been reported both in streptozotocin-induced diabetic rats and in the spontaneously diabetic BB rat. We have measured the levels of neuropeptide Y encoding messenger ribonucleic acid (mRNA) in both of these rat models to determine whether an increase in neuropeptide Y gene expression is a contributory factor to the increases in hypothalamic neuropeptide Y immunoreactive peptide content. In the hypothalami of both the spontaneously diabetic BB/E and the streptozotocin-diabetic animals, neuropeptide Y mRNA showed significant elevations (to 204 +/- 13% (+/- SE) and 387 +/- 48% of control values, respectively, p less than 0.01 for both). Our results demonstrate that two models of insulin-deficient diabetes in the rat are associated with increased hypothalamic neuropeptide Y mRNA. Taken with the known effects of neuropeptide Y on food intake these results suggest that increased neuropeptide Y synthesis in the hypothalamus may be related to the hyperphagia seen in the diabetic condition.