This study examined the relationship between longitudinal clinical course and sleep and cortisol findings in adolescent unipolar major depressive disorder (MDD). Subjects were 28 adolescents (15.4 +/- 1.3 years) systematically diagnosed with unipolar MDD and 35 group-matched normal controls who participated in EEG sleep and neuroendocrine studies. Follow-up clinical assessments were conducted 7.0 +/- 0.5 years later in 94% of the original cohort. Although initial group comparisons failed to show significant differences in biologic measures, analyses incorporating clinical follow-up reveal that changes in sleep and cortisol measures are associated with differential longitudinal course. Normal controls who would develop depression after the biologic studies had shown significantly higher density of rapid eye movements (REM) and a trend for reduced REM latency compared to controls with no psychiatric disorder at follow-up. Depressed subjects with a recurrent unipolar course showed a trend towards elevated plasma cortisol near sleep onset compared to MDD subjects with no further episodes during the follow-up interval.