It has been suggested that angiotensin-converting enzyme (ACE) inhibitors halt the progression of chronic renal failure. During the first months of a controlled trial of this hypothesis a fall in haemoglobin (Hb) was observed in patients treated with the ACE inhibitor enalapril. It was investigated whether this was related to changes in serum erythropoietin (EPO). Data were analysed in 59 consecutive patients during an observation period of 90 days. In enalapril-treated patients (n = 27) Hb fell gradually from a median value of 7.6 to 6.7 mmol/l at 90 days of treatment. In the control group of patients on conventional antihypertensive treatment (n = 32) median Hb was unchanged (7.6 mmol/l) throughout the observation period (p less than 0.001 enalapril vs control). In the enalapril-treated group median EPO concentration fell from 32 to 24 U/l at 90 days of treatment, whereas in conventionally treated patients median EPO was 34 U/l and 35 U/l, respectively (p less than 0.05 enalapril vs control). Neither glomerular filtration rate nor arterial blood pressure differed significantly in the two groups. Furthermore, there were no signs of bone marrow suppression, increased haemolysis or change in plasma volume. In conclusion, a decrease in Hb was found after start of treatment with enalapril in patients with progressive chronic renal failure, possibly caused by a suppression of EPO production.