A derangement of magnesium homeostasis with hypermagnesemia and increased intraerythrocyte Mg content [Mgi] has been described in uremic patients, and could play a pathogenetic role in both alterations of bone metabolism and vascular reactivity, observed in these patients. Recently Féray and Garay described in human erythrocytes a transport system which catalyzes outward Mg movements in the presence of external Na. These fluxes may be responsible for maintaining and regulating a low [Mgi]. The aim of this study was to evaluate in 16 normal subjects and 14 uremic patients undergoing CAPD: [Mgi] and rate of Na-dependent and Na-independent Mg efflux in Mg-loaded erythrocytes, in order to maximally stimulate Mg efflux. Mean plasma and intraerythrocyte Mg concentrations were significantly higher in CAPD than in normal subjects (1.09 +/- 0.20 vs 0.86 +/- 0.004 mmol/l, p less than 0.001 and 2.57 +/- 0.38 vs 1.96 +/- 0.18 mmol/l RBC, p less than 0.001). After an in-vitro Mg load, the intraerythrocyte Mg concentration and Na-independent Mg efflux were similar in both groups (17.5 +/- 1.4 vs 18.2 +/- 4.1 mmol/l RBC and 152 +/- 20 vs 126 +/- 19 mumol/l RBC/h). However, the Vmax of erythrocyte Na-stimulated Mg efflux was significantly higher in CAPD patients than in normal subjects (357 +/- 48 vs 229 +/- 88 mumol/l RBC/h, p less than 0.02). [Mgi] and the rate of Na-dependent Mg efflux were inversely related in CAPD patients (r = -0.76; p less than 0.002). These results indicate that uremic CAPD patients have a [Mgi] and Vmax of erythrocyte Na-dependent Mg efflux higher than normal subjects; this could reflect a compensatory, although insufficient, mechanism against high levels of intraerythrocyte Mg concentration, as suggested by the correlation between [Mgi] and the rate of Na-dependent Mg efflux.