Polycythemia and hyperhomocysteinemia are risk factors for thrombosis. Since red blood cells actively metabolize methionine to homocysteine, we investigated whether or not patients with polycythemia have increased plasma levels of homocysteine, which might contribute to their increased thrombotic risk. In ten patients with polycythemia, the plasma homocysteine levels were measured before phlebotomy, three days after the procedure and 1-2 months later. The baseline mean plasma homocysteine levels in patients (9.7 +/- 1.6 mumol/L [+/-SD]) did not differ significantly from that found in 30 sex- and age-matched healthy controls (12.2 +/- 6.9). Despite a fall in the patients' mean [+/-SD] hematocrit from 0.50 +/- 0.02 at baseline to 0.47 +/- 0.03 three days after phlebotomy (significant at 95%) and to 0.48 +/- 0.02 after 1 to 2 months (not significant), the mean plasma homocysteine levels did not change significantly (9.9 +/- 2.3 mumol/L at 3 days and 9.7 +/- 2.1 mumol/L at 1-2 months). It is unlikely that high plasma homocysteine levels contribute to the increased thrombotic risk of polycythemic patients.