Recent studies have suggested a role for nitric oxide (NO) in the regulation of food intake. The obese (ob/ob) mouse is a genetic model of obesity. Previously, it has been demonstrated that ob/ob mice show a marked weight reduction when treated with a nitric oxide synthase inhibitor. In the studies reported here, we demonstrate increased levels of nitric oxide synthase (NOS) and its mRNA in the hypothalamus of genetically obese (ob/ob) mice compared to their lean littermate controls (ob/c). NOS levels were 0.016 +/- 0.001 nmol/mg/min in ob/ob compared to 0.009 +/- 0.001 in ob/c (p < 0.01) and NOS mRNA was 32.0 +/- 5.0 pg NOS mRNA/mg total RNA in ob/ob compared to 12.4 +/- 4.0 in ob/c (p < 0.05). These studies further support the possibility of a role for nitric oxide in the regulation of food intake.