Major Depression of the most common, unipolar, type is an important human disorder of unknown pathophysiology. Several kinds of evidence implicate chronobiological mechanisms: cyclicity of the mood disturbance in some patients, diurnal mood variation, associated severe sleep maintenance difficulty, REM sleep timing abnormality, temporary remission of symptoms with total sleep deprivation, early sleep termination, or REM sleep deprivation. As to mechanism, the most current possibilities include phase advance of several rhythms relative to sleep, short period of the oscillator undelrying those rhythms, and a sensitive phase of the circadian cycle during which sleep is depressogenic. It is emphasized, however, that no direct evidence of a chronobiologic disorder in unipolar depression has yet been obtained. In preliminary work, 3 depressed female outpatients have been studied and compared with 3 control subjects. One depressive showed nightly short REM latencies, but none gave evidence of phase advance of the body temperature or serum cortisol rhythms relative that of to sleep. Seventeen female subjects will be studied in two age groups (20-35 and 50-65), in addition to 3 subjects studied previously. The experiment will be conducted in a time isolation laboratory equipped to record the following on a round-the-clock basis: sleep stages, body temperature, frequent serum samples of cortisol, growth hormone and melatonin, subjective activation, and mood, psychomotor performance and various activities of daily living. Subjects will be entrained to a 24 hour routine for 7 calendar days, followed by "free running" for 10 additional days. The studi is expected to reveal: any abnormalities of circadian periods or phase angles between the sleep-wakefulness, temperature, cortisol, melatonin and other rhythms; the relationship of short REM latency to the phase of overall REM propensity; whether and why body temperature is elevated in depression; and the morphology of the cortisol secretory pattern.