Administration of cobaltic protoporphyrin IX (CoPP) into the third ventricle of the brain by intracerebroventricular injection in rodents is known to result in transient hypophagia and remarkably prolonged weight loss. The mechanism of action of CoPP in eliciting these effects is unknown. It is known that nitric oxide plays a role in food intake and that the hyperphagia that results from a wide variety of genetic, physiological, and pharmacological stimuli can be blocked by the administration of inhibitors of the enzyme nitric oxide synthase (NOS). We demonstrate that intracerebroventricular administration of compounds that alter nitrergic tone can also change food ingestion and weight gain patterns in normophagic rats. We also demonstrate that CoPP decreases NOS activity but that it paradoxically increases neuronal NOS transcript expression and increases neuronal NOS protein content on Western blotting.