OBJECTIVE: To elucidate the types of problems encountered during implementation of a World Wide Web-based clinical practice guideline to manage hyperbilirubinemia in newborn infants. DESIGN: Formative assessment of an automated clinical-practice guideline in a large-scale implementation. SETTING: Primary-care clinics and offices, inpatient clinics, and emergency department affiliated with an academic children's hospital. PARTICIPANTS: General pediatricians, neonatologists, pediatric nurses, and computer scientists. RESULTS: Existing guidelines for hyperbilirubinemia management could not be translated directly into web pages. Modifications of the original guidelines were required to represent the clinical intent of the guidelines accurately. In addition, the automated guideline was augmented to incorporate a mechanism for generating clinical encounter forms in order for the system to be accepted into the clinical work flow. Other clinical considerations that influenced the final form of the automated guideline included limitations of computer resources and time constraints during patient encounters. CONCLUSIONS: Many existing guidelines are not amenable to straightforward implementation in automated systems. Strategies to increase the efficacy of the automated guidelines included guideline modifications, as well as careful consideration of the flow of clinical work. Repeated cycles of development and pilot testing are needed to design methods to accommodate the constraints imposed by clinical use.