1. Whole blood histamine content was measured in 80 patients with myeloproliferative disease. Increased levels were found in 60 per cent of patients with uncontrolled polycythemia vera, in 7 per cent of patients with polycythemia vera being controlled by myelosuppressive therapy, and in 71 per cent of a group with "spent" polycythemia, myeloid metaplasia and myelofibrosis.

2. The excretion of histamine in the urine was measured in 60 patients, 30 with elevated blood histamine and 30 with normal blood histamine. The urine findings paralleled the blood findings in 90 per cent of the cases.

3. Measurements of cell-poor and cell-rich fractions of blood showed that the histamine is contained in the white cell fraction. Elevated basophil counts were present in 50 per cent of the patients and occurred with the greatest frequency in the groups with elevated blood and urine histamine. A rough correlation between the basophil count and the histamine content of blood and white cell fractions was observed in normal subjects and most cases with myeloproliferative disease. Data obtained in some cases of myeloproliferative disease suggest that the histamine content of the basophil may be abnormal and that other granulocytes may contribute to the total leukocyte histamine.

4. Myelosuppressive agents produced a reduction in histamine (expressed per 109 myeloid cells) and a decrease in urine histamine as control of the myeloproliferative process was achieved. Treatment with phlebotomy alone produced no change in histamine levels.

5. The incidence of pruritus, upper gastrointestinal distress and urticarial manifestations was increased 7-fold, 4-fold and 12-fold, respectively, in patients with elevated histamine levels as compared with those who had normal histamine levels.

6. Cyproheptadine, a potent antihistaminic, successfully controlled pruritus, relieved pyrosis and suppressed urticarial eruptions in patients with elevated histamine levels. Suppression of the reaction to subcutaneously administered codeine (a histamine-releaser) afforded objective evidence that cyproheptadine blocked the effects of histamine release in vivo.

7. The metabolism of histamine and the role of elevated histamine levels in the clinical manifestations and pathophysiology of myeloproliferative disease are discussed.

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