Implementation of guidelines offers one of the largest opportunities for quality improvement, utilization review, and cost control for the health-care enterprise. If guidelines could be implemented on a large scale, their adoption could result in $100 billion in annual savings as well as improve the quality of patient care. However, infrastructural barriers impede progress. Collaboration between the Laboratory Medicine Health Services Program at the University of Alabama at Birmingham, Columbia-Presbyterian Medical Center, and the Cerner Corporation, funded by the National Institute of Standards and Technology as part of the Advanced Technology Program involving ¿Information Infrastructure for Healthcare,¿ is focused on developing and delivering: 1) methods for creating operational forms of guidelines; 2) an effective computer-based architecture for implementing guidelines in clinical practice; 3) methods for packaging guidelines for wide distribution; 4) methods for testing the efficacy, safety, and acceptability of guidelines; and 5) a model for collecting, aggregating, and normalizing data from disparate systems. This hypothesis-driven research program is focused on laboratory medicine-based guidelines as a tool for developing, testing, and evaluating methods that can be implemented widely.