Twenty-one percent (20/97) of patients with an episode of major depressive disorder and no history of chronic minor depression who sought treatment at five university medical centers had not recovered after two years of prospective follow-up. The rate of recovery was highest in the three months after entry into the study, with a notable decrease in rate after one year. Most patients who did not recover had severe depressive symptoms throughout the two years of follow-up. Long duration of episode before entry into the study, inpatient hospitalization status at entry, intact marriage, low family income, admitting research center, and a history of nonaffective psychiatric disorders (including alcoholism) predicted a chronic course. The implications of these findings for clinicians, researchers, and public health planners are discussed.