DXplain is an evolving computer-based diagnostic decision-support system designed for use by the physician who has no computer expertise. DXplain accepts a list of clinical manifestations and then proposes diagnostic hypotheses. The program explains and justifies its interpretations and provides access to a knowledge base concerning the differential diagnosis of the signs and symptoms. DXplain was developed with the support and cooperation of the American Medical Association. The system is distributed to the medical community through AMA/NET—a nationwide computer communications network sponsored by the American Medical Association—and through the Massachusetts General Hospital Continuing Education Network. A key element in the distribution of DXplain is the planned collaboration with its physician-users whose comments, criticisms, and suggestions will play an important role in modifying and enhancing the knowledge base. © 1987, American Medical Association. All rights reserved.