Background and Objectives: While content, navigability, and usability are essential qualities of effective Web sites, the health care literature contains limited discussion of these issues. This article describes how knowledge gained through focus groups, Web site searches, and individual interviews were used to develop and improve a health-related Web site. Methods: We conducted 10 focus groups and searches of existing Web sites in preparation for developing a Web site about colorectal cancer (CRC) screening. We conducted 30 in-depth interviews to assess content, navigation, and usability of a new CRC Web site, using participants recruited from Michigan communities with a low incidence of CRC testing. Targeted participants were 50-70 years of age, had no prior experience with CRC testing, and had variable comfort levels with Internet use. Results: Existing CRC screening Web sites uniformly use user-directed navigation and have little variation in content. Our study participants stimulated revisions in content, navigation, and usability. Revised content factors included comprehension, utility, and appeal. Navigation changes focused on logical transition between sections. Usability changes included user focus and clarity of graphics/ text. Conclusions: We found focus groups, Web site searches, and individual interviews useful in developing and testing content, navigation, and usability of a CRC screening Web site. These steps provide methodological procedures for developing and revising health-related Web sites.