The effects of angiotensin converting enzyme (ACE) inhibitors and their combined use with an antiestrogenic steroid on erythropoiesis were investigated in patients on chronic hemodialysis (CHD). Hematocrit was decreased by 10% or more in 6 of 12 patients who received either captopril or enalapril for 2-6 months. Erythropoietin (Epo) and angiotensin II (AII) were significantly reduced in these patients. When treatment with mepitiostane was combined with ACE inhibitor, anemia was significantly improved but without evidence of changes in circulating Epo concentrations or indices of renin-angiotensin activity. The reduction of AII and Epo formation by ACE inhibitors seems to play an important role in the worsening of anemia in patients on CHD; addition of an antiestrogenic steroid should be considered.