Background. A Dutch cohort of predominantly out-patient DSM-III-R major depressive patients was followed for 3 to 5 years after start of treatment in a psycho-neuro-endocrinological prediction study. The study design permitted description of the course of remissions, relapses and recurrences. Methods. Pharmacological treatment was standardized, psychotherapy was tailored to the needs of the patient, follow-ups were done monthly until 3 years or more after the initial recruitment. Results. After 9 months 49% of the patients had reached full remission and 45% were in partial remission. During the following 3 to 5 years 82% of the patients had reached a period of full remission. Sixteen per cent of the patients needed 2 years or more before full remission. A relapse or recurrence rate of 41% within 5 years was found. Patients with residual symptoms relapsed particularly in the first 4 months after remission, while patients without residual symptoms recurred mainly after 12 months after remission. Previous depressive episodes and psychoticism predicted relapse. Psychomotor retardation at inception predicted a longer time to partial remission. Conclusion. In most cases, major depression is a seriously impairing episodic disease. This is also true for a sample of predominantly out-patients treated at a university clinic.