Objective: This study evaluated the effects of a national interdisciplinary faculty development program, Project MAINSTREAM, on creating curriculum enhancement in health professional education. Method: Thirty-nine faculty completed a two-year, part-time fellowship program featuring interdisciplinary collaboration, mentoring, training meetings, and Internet-based instructional materials. The main vehicle for curricular change was a required collaborative education project to develop trainees' core competencies in substance abuse prevention services. Results: Fellows used a variety of approaches to implement 123 curricula and provide 66,995 hours of training to 10,170 trainees. Ninety percent of the training hours occurred in required courses, a potential indication of sustainability. Fellows indicated that a majority of the offerings would be sustained beyond the fellowship. Conclusion: Project MAINSTREAM shows promise as a model for achieving durable curriculum change in response to the public health crisis associated with a workforce untrained to deliver substance abuse services. (Contains 1 figure and 4 tables.)