Diffuse hypothalamic-hypopituitarism complicating viral meningoencephalitis has been rarely documented. In this report, we describe the syndrome in a 41 yr old male and review the literature. Detailed endocrine studies were performed 1 month after the onset of apparent viral encephalitis. Repeated 08:00 h serum cortisol levels were low, but increased after administration of lysine-vasopressin. Urine 17-hydroxy-corticosteroid (17-OHCS) values rose with prolonged cortrosyn infusion, but failed to respond after administration of metyrapone. Serum thyroxine was decreased; basal levels of serum thyrotropin were low-normal, but there was a prolonged response to tyrotropin (TSH) to thyrotropin releasing hormone (TRH). Basal prolactin was elevated with a minimal response after TRH. Testosterone and gonadotropins were both diminished, and gonadotropins increased (but less than in normal subjects) after injection of gonadotropin releasing hormone (LHRH). The overnight water deprivation test confirmed the presence of diabetes insipidus. In the present context, the abnormal endocrine investigations were strongly supportive of disturbed hypothalamic activity. Hypothalamic-hypopituitarism following viral meningoencephalitis may occur more frequently than previously reported, and thus basal pituitary function should be assessed in all patients with viral meningoencephalitis.