In 1999, the American Osteopathic Association approved plans for “substantive change” to the medical curriculum at Lake Erie College of Osteopathic Medicine (LECOM) in Erie, Pa. In addition to the school’s traditional, lecture-based curriculum, LECOM sought to create alternative—but distinct—learning pathways: independent study (described elsewhere) and problem-based learning (PBL). After selecting a long-standing, successful PBL program to guide our efforts and after a 1-year period of planning, developing, piloting, and refining the program, we introduced PBL in the 2000-2001 academic year. This learning pathway consists of carefully constructed cases that allow for progressive disclosure across group-tutorial sessions, from patient presentation to diagnosis and management. With more than 5 years of data on student performance and evaluations, LECOM can investigate the merits of its three basic science learning pathways. The description of LECOM’s longitudinal database will allow program evaluators to assess and compare each of the three basic science learning pathways.