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This study examined the direct effects of physical and sexual abuse, neglect, poor family communication and worries concerning family relationships, depression, anxiety, and dissociation on posttraumatic stress symptoms. Runaway youth were recruited from emergency youth shelters in New York and Texas. Interviews were completed with 350 youth who averaged 15 years of age. Structural equation modeling was used to examine family functioning, maltreatment, depression, dissociation, and anxiety in relation to posttraumatic stress symptoms. Results indicated that direct effects of family relationship worry to dissociation, β = .77, p < .001; depression, β = .85, p < .001; and anxiety, β = .90, p < .001 were significant, as were relationships between family communication and youth dissociation, β = .42, p < .001; depression, β = .46, p < .001; and anxiety, β = .32, p < .001. No significant effects of physical/sexual abuse or neglect were found. Higher levels of dissociation, β = .21, p < .001 and anxiety symptoms, β = .34, p = .01 were positively and significantly associated with posttraumatic stress symptoms, but depression was not. Findings underscore the critical role of family relationships in mental health symptoms experienced by runaway adolescents.