ACCESS (A Case Control Etiologic Study of Sarcoidosis) was funded by the National Institutes of Health and collected data on 704 newly diagnosed, biopsy-proven cases of sarcoidosis and control subjects matched by age, sex, race, and geographic area. The goal of this study was to generate hypotheses about the etiology of sarcoidosis. The major hypothesis of the ACCESS investigators was that sarcoidosis occurs in genetically susceptible individuals through alteration in immune response after exposure to an environmental, occupational, or infectious agent. Strict criteria were used for the diagnosis of sarcoidosis and definitions of specific organ involvement were developed. The patients recruited for ACCESS represent the best clinical description of sarcoidosis at presentation in the United States. The study investigated the following: occupational/environmental triggers using a detailed questionnaire, infectious agents in the blood by polymerase chain reaction of 16s rDNA of microorganisms and cultures for cell wall-deficient mycobacteria, and genetic associations using a questionnaire to determine familial aggregation and candidate gene analysis. No single cause of sarcoidosis was identified. The results of this study are reviewed and possible lessons learned are discussed.