Synaptosomal [H-3]norepinephrine (NE) uptake of hypothalamus was measured in genetically obese (ob/ob) and diabetic (db/db) mice. Synaptosomal [H-3]NE uptake of (ob/ob) mice was significantly decreased compared with that of their lean littermates. Synaptosomal [H-3]NE uptake of db/db mice was also lower than that of lean mice, although the degree of reduction in NE uptake was greater in ob/ob mice. The present study suggests that reduced NE reuptake of hypothalamus may be involved in the hyperphagia of genetically obese and diabetic mice.