This study describes the effect of a chronic decrease in hematocrit on blood pressure, cardiac output (CO), total peripheral resistance (TPR), and plasma volume in spontaneously hypertensive rats (SHR), and all but plasma volume in normotensive Wistar rats (NWR). Hematocrit was decreased by treatment with either heparin, vitamin K inhibitor ( pelentan ), or by repeated blood letting (BL). The results show that in SHR, a decrease in hematocrit, regardless of how produced, was associated with a significant decrease (p less than 0.01) in blood pressure. Prevention of heparin-induced decrease in hematocrit by repeated transfusions of red blood cells abolished the blood-pressure-lowering effect of heparin. By using combined data on hematocrit and systolic blood pressure in all five SHR groups, a significantly positive correlation and linear regression between hematocrit and blood pressure were obtained. When compared to control untreated SHR, heparin- or pelentan -treated SHR showed a significant (p less than 0.001) decrease in TPR and a significant increase in CO, while in SHR BL, no difference in TPR or CO was found. Plasma or blood volume did not differ among the groups. In NWR, heparin treatment resulted in significantly decreased hematocrit, decreased TPR, and increased CO compared to control normotensive rats. However, blood pressure did not change. Results confirming the authors' previous study and those of other investigators indicate a direct association between hematocrit and systemic hypertension. Lowering the hematocrit can effectively lower an elevated blood pressure. Moreover, the data suggest that heparin or pelentan induces a vasodilator effect that cannot be attributed to a decrease in hematocrit alone.