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What are the challenges involved in designing, modifying, and improving a major health information portal that serves over sixty million page views a month? MedlinePlus, the National Library of Medicine's (NLM's) consumer health Website, is examined. Challenges are presented as six "studies," which describe selected design issues and how NLM staff resolved them. Improving MedlinePlus is an iterative process. Changes in the public user interface are ongoing, reflecting Web design trends, usability testing recommendations, user survey results, new technical requirements, and the need to grow the site in an orderly way. Testing and analysis should accompany Website design modifications. New technologies may enhance a site but also introduce problems. Further modifications to MedlinePlus will be informed by the experiences described here.