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This study examined reciprocal relationships between posttreatment substance use and psychiatric symptoms in adolescents with both a substance use disorder and an Axis I mental health disorder. Participants (13–18 years old) were recruited from inpatient treatment centers and interviewed during treatment and monthly for 6 months. Participants who relapsed (N = 103; 48% female) reported the incidence and severity of psychiatric symptoms experienced before and after their 1st posttreatment substance use. The number of symptoms and depression symptoms experienced were related to use of stimulants and other drugs during relapse. There was evidence for both self-medication (symptom reduction) and rebound (symptom exacerbation) effects of substance use on symptom severity. These results demonstrate that, for adolescents with both substance use and mental health disorders, psychiatric symptoms are 1 factor influencing posttreatment substance use.