To verify the hypothesis of an early impairment of erythropoietin (Epo) production and to assess the adequacy of its circulating levels in diabetic nephropathy, we investigated Epo values in 18 microalbuminuric type 2 diabetic patients with normal renal function (7 anaemic and 11 nonanaemic), 24 subjects with uncomplicated iron-deficiency anaemia, and 15 healthy controls comparable for sex and age. Mean+/-S.D. plasma Epo level was 56.4+/-12.7 mU/mL in iron-deficient patients and 9.3+/-2.6 mU/mL in controls. In diabetic groups, mean+/-S.D. Epo level was 11.38+/-3.65 mU/mL in nonanaemic and 49.12+/-6.44 mU/mL in anaemic subjects. No significant difference (P>.05) in Epo values was found between controls and nonanaemic diabetic patients. Anaemic diabetics and iron-deficient subjects had significantly higher values than the nonanaemic groups (P>.001). An inverse significant relation between Epo levels and Hb concentration resulted in both anaemic diabetics (r=-.44, P>.05) and iron-deficient patients (r=-.61, P=.001). Analysis of covariance (P>.05) and comparison of the two regression lines (t=0.4, df=29, P>.05) did not show any significant difference between diabetic patients with anaemia and iron-deficient patients. These results suggest that normochromic anaemia observed in microalbuminuric diabetic patients with normal renal function is not due to Epo deficiency, and circulating levels of this hormone are suitably increased with regard to Hb concentration.