In 1963 Coppen and Shaw reported that patients with manic-depressive psychosis showed, on clinical recovery, a significant decrease in exchangeable sodium, and in residual sodium (exchangeable minus extracellular sodium), presumed intracellular, per litre of body water. Coppen, Shaw, Malleson and Costain (1966) found a similar type of shift in mania but the deviation from normal was, on average, more extreme. Although low and high sodium diets had no effects on the distribution of sodium in manic-depressive psychotics, the administration of spironolactone resulted in a significant reduction of residual sodium (Coppen, 1970). The possible involvement of aldosterone in these changes led Jenner et al. (1967) to examine aldosterone excretion in a 48-hour cycle patient and Murphy, Goodwin and Bunney (1969) to examine groups of manic and depressed patients. Murphy et al. found lower rates of excretion of aldosterone in depression than in mania, but Jenner et al. found the opposite.