Dopamine-beta-hydroxylase (DBH, EC 126.96.36.199) is the enzyme responsible for the final step in norepinephrine biosynthesis and recently the development of a sensitive assay system has permitted the detection of DBH activity in serum, brain and other tissues. Wise and Stein were the first to report a significant DBH activity reduction in post-mortem brains obtained from chronic schizophrenic patients. After this report, several studies were performed on serum DBH activity in schizophrenic subjects without any consistent results. In this study we examined plasma DBH activity in 14 chronic schizophrenic in-patients (4 males and 10 females, 40.6±8.3 years). The patient plasma DBH activities were investigated twice at intervals of 12 months and compared with normal volunteers. The volunteers were 12 laboratory personnel (6 males and 6 females, 31.5±11.6 years) in the first control group, and 12 laboratory personnel (6 male and 6 females, 30.6±7.2 years) in the second control group. Five of the same laboratory personnel (3 males and 2 females) were tested in both control groups. Plasma DBH activity was determined according to the photometric assay by Nagatsu and Udenfriend using tyramine as substrate. DBH activity was expressed in international units (μmol/min)/liter plasma (I.U./L.). Statistical comparisons were made with two-tailed Students' t-test. DBH activities ranged widely from 3.0 to 34.0 I.U./L. (in the first determination) and from 2.2 to 29.9 (in the second) in the schizophrenic group, while ranging from 6.4 to 39.3 (in the first) and from 0.1 to 39.9 (in the second) in the control group. The two mean values of patient plasma DBH activity (16.0 in the first and 15.7 in the second) were insignificantly lower than the corresponding control values (22.1 in the first and 20.4 in the second). There was no difference between the two mean values of plasma DBH activity in the schizophrenic group. A consistent tendency for higher plasma DBH activity was recognized in females than in males both in the control and in the schizophrenic group. The plasma DBH activity of individual subjects both in the schizophrenic group and in the control group who had two determinations at intervals of 12 months, showed rather great variations (50% decrease to 150% increase in the schizophrenic and 58% decrease to 66% increase in the control) over one year period without any appreciable psychological and psychotic changes. We failed to find any abnormal levels of DBH in chronic schizophrenic plasma whereas Wise and Stein observed a reduced DBH activity in chronic schizophrenic brains. No relationship between plasma (or serum) DBH activity and brain DBH activity would be expected on the basis of our study and other previous works.