Dopamine-beta-hydroxylase (DBH) activity is increased at least 5-fold in the serum of rats with experimental diabetes produced by Streptozotocin or Alloxan. The increased DBH activity persisted for 7 months. Dialysis did not reduce the elevated activity. Based on a large increase in the maximal velocity of the enzyme reaction and immunoprecipitation studies, there appears to be increased amounts of DBH in the serum of diabetic rats. Thyroxin and triiodothyronine concentrations were reduced in diabetic serum but replacement doses of these hormones did not correct the high DBH activity. In contrast, adrenalectomy or insulin administration prevented the diabetes and elevations of circulating DBH. Circulating norepinephrine levels in arterial and venous blood were measured at 4 and 16 weeks after the onset of diabetes and elevated only in venous blood at the early time interval. In summary, circulating DBH levels were increased in experimental diabetes but did not correlate with circulating norepinephrine levels. Further studes are required to differentiate between the possibilities of increased sympathetic nervous system activity and altered DBH turnover in experimental diabetes.