Background: PCPs must make appropriate referrals and use complex medical genetics information and testing in daily patient care. Since the early 1980's clinical geneticists have used knowledge-bases such as the Online Mendelian Inheritance in Man (OMIM™), the HELIX™ Directory of Molecular Laboratories, and Reprotox™, together with expert systems like the London Dysmorphology™ Database in patient care. Combining these experiences with new information about how physicians use computer resources, we developed a decision-support tool called INFOGENETICS. This resource assists the PCP to: (1) Search OMIM Titles and the Birth Defects Encyclopedia Index to generate a differential diagnosis to determine, “Could my patient's problem have a genetic basis?” (2) Search a directory of over 300 genetics centers, state genetics coordinators, Newborn Screening Programs and Children's Specialty Clinic Coordinators. (3) Obtain laboratory test information about how to submit a sample for a specific genetics test? (4) Search a directory of over 200 genetic support organizations.Methods: We performed usability studies in pilot projects with PCPs over two years at 10 sites including private practices, Title V funded Community Health Centers, pediatric resident clinics, hospital clinics, and Children with Special Health Care Needs Clinics in the Southeastern and Middle Atlantic Genetics Regions. Data consisted of pre- and post-use questionnaires and audit trails embedded in the software. Initial on-site training about genetics and the use of the computer software progressed to brief telephone instruction with a simplified, ”user-friendly“ software package.Results: Numerous revisions of the software were implemented as a result of these studies. Initial data analysis revealed that in using INFOGENETICS, physicians became aware of the wide variety of Medical Genetic problems in their practice, increased contacts with the local genetics centers, and retrieved genetics laboratory testing information for patient care. Nurses frequently accessed information about patient resources; physicians expressed a desire for clinical care guidelines and expert diagnostic information that are currently being incorporated into the software. Conclusions: Our experience working with primary care providers as they used, INFOGENETICS, has resulted in the development of user-friendly software and a World Wide Web application that can facilitate the application and use of medical genetics information in daily patient care.