The Medical Specialty Preference Inventory (MSPI; Zimny, G.H. (1979). Manual for the Medical Specialty Preference Inventory. St. Louis, MO: St. Louis University School of Medicine), a measure of medical students' interests, was substantively and empirically examined to identify an underlying factor structure. A factor model for the original MSPI based on 38 factors in five general areas was evaluated on a national sample of 1014 medical students and yielded poor fit to the data. Exploratory factor analyses at the item level utilizing the full pool of MSPI items produced an 11 factor solution with 88 items. Sub-scales were identified within this model and an 11-18 higher-order model and an 18 sub-scale model also were proposed. The relative fits of the three models were evaluated by confirmatory factor analysis with the 18 sub-scale model shown to be superior. This model was cross-validated on a separate sample of 1016 medical students and fit the data well. All sub-scales exhibited adequate internal consistency across samples. These findings support the need for a revised MSPI based on 18 scales. Implications of these findings for MSPI scoring practices are discussed along with future directions. (Contains 4 tables.)