The therapeutic effect of total sleep deprivation (SD) given twice a week, for 4 weeks, was investigated in 16 drug-free patients with major affective disorders. The response was excellent in five patients, satisfactory in three and minimal in eight patients. Six of these patients were treated prophylactically once a week, and four had an excellent response. Additionally, out of five normothymic drug-free patients with affective illness treated prophylactically with SD, without prior therapeutic SD treatment, three had an excellent response. The majority of responders were rapid cycling patients. This method is worth applying to patients resistant to classical treatment.