Ouabain-sensitive Na+-K+-stimulated ATPase was measured in red cell membranes using a spectrophotometric assay. The mean enzyme level in patients in the depressed state (1.2 nM/mg protein per min +/- 0.18 SEM) was lower lower than that in well-state patients (2.0 +/- 0.26) and hypomanic patients (2.4 +/- 0.31). Lithium treatment itself did not alter ATPase levels. Levels in patients in the well state were not significantly different from controls and thus ATPase does not constitute a "trait" marker for affective illness. Plasma cortisol level was higher in well-state patients (15.9 micrograms/dl +/- 1.46) than in controls (11.5 +/- 0.75). There were no significant differences in cortisol in these single morning samples during different mood states. Cortisol level correlated negatively with ATPase level in the total group of patients (r = 0.42, p less than 0.005), especially in those who were euthymic. These data indicate a relationship between cortisol and ATPase levels in affectively ill patients. Ouabain-sensitive NaK ATPase may be useful as an indicator of state in affective illness; plasma cortisol may be continuously elevated in some individuals with affective disorder.