The Canadian Erythropoietin Study Group conducted a randomized, placebo-controlled trial to examine the effect of human recombinant erythropoietin on the treatment of anemia in 118 hemodialysis patients. The effectiveness of therapy on hemoglobin concentration and quality of life has been reported elsewhere. Herein is reported the effect of erythropoietin therapy on blood pressure. Patients receiving erythropoietin had a significant increase in diastolic blood pressure (DBP; p = 0.001) and required increased antihypertensive medication. There was no difference in the incidence of severe hypertension (DBP greater than 110 mm Hg or hypertension-related seizure) between placebo-treated patients (13%) and those receiving erythropoietin (14%). The development of severe hypertension in erythropoietin-treated patients was associated with a history of receiving antihypertensive medication or having native kidneys in situ. In the first 5 weeks of the study, there was a correlation between the change in hemoglobin concentration and the change in DBP (r = 0.42, p less than 0.001). Although erythropoietin therapy was associated with a significant increase in DBP, there was no difference between placebo- and erythropoietin-treated patients with respect to severe hypertension or hypertension-related seizures.