OBJECTIVE To explore residents' competency in medical knowledge and in empathy, one element of professionalism, and to evaluate the relationship between competencies in these domains. METHODS In 2003-2004 and 2004-2005, first-year internal medicine residents at the Mayo Clinic College of Medicine in Rochester, Minnesota were invited to participate in a prospective, longitudinal study of resident competency. Participating residents completed the annual Internal Medicine In-Training Examination (ITE) each October and the Interpersonal Reactivity Index (IRI), a standardized tool to measure empathy administered at multiple time points during training. Changes in medical knowledge and empathy between the fall of postgraduate years one and two were evaluated, and associations between medical knowledge and empathy were explored. RESULTS Residents' medical knowledge as measured by the ITE increased over the first year of training (mean increase 8.7 points, P < .0001), whereas empathy as measured by the empathic concern subscale of the IRI decreased over this same time period (mean decrease 1.6 points, P = .0003). No significant correlation was found between medical knowledge and empathy or between changes in these domains of competency over time. CONCLUSIONS Resident competency in the domains of medical knowledge and empathy seems to be influenced by separate and independent aspects of training. Training environments may promote competency in one domain while simultaneously eroding competency in another. Residency programs should devise specific curricula to promote each domain of physician competency.