While even a single episode of depression is disabling and entails considerable economic loss and emotional suffering, recurrent depression represents a major public health problem. Effective treatments are available for the acute episode of depression, but relatively few clinical trials have been conducted on the maintenance treatment or prevention of subsequent episodes. Until now, maintenance treatment for recurrent unipolar depression has focused exclusively on the implementation of somatic therapies with only moderate success. We have over the last four years begun an investigation of psychological and combined treatments in comparison with somatic treatments alone. During the next five years, we expect to achieve the following major research goals: 1) to determine whether active, long-term (3 year) drug treatment (imipramine in combination with psychotherapy (Maintenance Interpersonal Psychotherapy) is superior to active drug treatment alone or psychotherapy alone or in combination with placebo (ongoing Study I); 2) to determine whether patients who do experience a recurrence or illness in a non-medication condition (i.e. no pill or placebo) in Study I, require 100% of their acute treatment dose or can be successfully maintained on 50% of that dose (Study II); 3) to ascertain whether those patients who survive three years of maintenance treatment in Study I without a recurrence can then be withdrawn from medicatIon without experiencing an recurrence in the subsequent two years (Study III); 4) to ascertain whether changes in selected biological, psychosocial, and clinical signs precede or are associated with recurrence of illness in unipolar patients.