In thalassemia erythrocyte cation permeability is increased, but the increment in ATPase-dependent cation pumps maintains normal concentrations of Ca++, Na+ and K+. In this study we investigated erythrocyte concentrations of Mg++ in heterozygous beta-thalassemia and in microcytic sideropenic anemia. Twenty-five healthy controls, 40 heterozygous beta-thalassemics and 25 patients with sideropenic anemia were studied. Erythrocyte Mg++ was assayed either by atomic absorption or by standard laboratory methods. Erythrocyte Mg++ was significantly lower in the beta-thalassemia group than in the other two groups (p less than 0.001). Serum magnesium was significantly lower in sideropenic anemia patients than in beta-thalassemics and in controls (p less than 0.01), whereas these latter two groups showed similar values. Our results suggest that the increment in ATPase-dependent cation pumps is not sufficient to maintain normal erythrocyte Mg++ concentrations in heterozygous beta-thalassemia. In sideropenic anemia cation permeability is not increased, therefore erythrocyte Mg++ is normal. Low serum Mg++ levels in sideropenic anemia could be explained by a primary Mg++ deficit associated with sideropenia.