The effect of subcutaneous and intraperitoneal administration of recombinant human erythropoietin (rHuEPO) on blood pressure was evaluated in 20 patients with renal failure on continuous ambulatory peritoneal dialysis. The two groups of patients were commenced on a 16-week course of twice weekly rHuEPO by either the subcutaneous (10 patients) or the intraperitoneal route (10 patients). One patient in the latter group was subsequently excluded because of operation and transfusion. The hemoglobulin increased significantly from 6.9 +/- 0.3 g/dl to 9.8 +/- 0.6 g/dl after subcutaneous rHuEPO treatment (p less than 0.01) at an average dose of 84 +/- 9 U/kg body weight/week. For the intraperitoneal group, despite a higher average rHuEPO dosage (133 +/- 7 U/kg body weight/week), the hemoglobin level was not significantly altered (7.0 +/- 0.4 g/dl to 8.0 +/- 0.4 g/dl, p less than 0.05). During the 16-week period of rHuEPO therapy, an increase in antihypertensive therapy was required more frequently in patients in the intraperitoneal group but the difference between groups failed to reach statistical significance. There was no conclusive evidence that the rise in hematocrit was an independent precipitant of hypertension. Patients who were hypertensive prior to rHuEPO therapy appeared most susceptible to the pressor effects in that 8 of 11 treated hypertensive patients required more intensive antihypertensive treatment during EPO administration whereas none of the untreated patients developed hypertension during the study (Fisher's exact test, p = 0.007). Plasma levels of the vasoactive hormones, atrial natriuretic peptide (ANP), plasma renin activity (PRA), and endothelin (ET) remained unchanged during both subcutaneous and intraperitoneal rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)