Two longitudinal studies conducted in Israel examined antecedents and outcomes of teacher depersonalization, a relatively understudied dimension of teacher burnout. Study 1 explored the outcomes of depersonalization. We predicted that depersonalization would predict classroom disruption, and that an aspect of intrinsic orientation for teaching, teacher enthusiasm, would mediate this relation. Study 2 explored the antecedents of depersonalization. We predicted that another aspect of intrinsic orientation for teaching, teacher autonomous motivation, would moderate the relation between organizational (principal and peer) support and teacher depersonalization. In Study 1, multilevel analysis of data from 73 middle school teacher-class pairs (1,792 students) showed that teacher depersonalization at the beginning of the year (Time 1) predicted end-of-year (Time 2) student and teacher reports of disruptive student classroom behaviors via teacher enthusiasm for teaching. In Study 2, 333 teachers reported on depersonalization at Time 1 and Time 2, on perceptions of principal support and sense of community at Time 1, and on autonomous motivation for teaching at Time 2. The predicted associations between organizational variables and Time 2 depersonalization were moderated by autonomous motivation for teaching; only to the extent that teachers' autonomous motivation was high did principal support and sense of community protect against depersonalization. Results highlight the importance of studying depersonalization as a distinct and maladaptive interpersonal phenomenon. They also suggest the important role of intrinsic orientation for teaching in preventing teacher depersonalization.