The Vmax of erythrocyte sodium-magnesium exchange was measured for the first time in 63 patients suffering from affective disorders and compared to that in 33 healthy subjects. Depressed patients had a significantly higher Vmax (215 +/- 13 vs. 151 +/- 14 mumol/l.cells/h; p < 0.005; mean +/- SEM). This tendency was conserved after division of the 63 patients into three clinical subgroups according to the DSM-III-R criteria. Thirty-four patients from this panel were divided into three subgroups according to the chemical class of the antidepressant drug used and were followed up during a 3-month period of drug treatment. Mood improvement over the 3-month period was associated with a slow increase in Vmax of Na/Mg exchange (delta increase approximately 25 mumol/l.cells/h), except in the subgroup of patients treated with non-tricyclic antidepressants (n = 8). These results are consistent with the previously reported link between high erythrocyte magnesium content and affective disorders. Indeed, enhanced Na/Mg exchange Vmax, which probably results from an increased number of transport units per cell, contributes to the normalization of red blood cell magnesium content correlated with mood improvement.