In 2006, the Centers for Disease Control and Prevention published guidelines for routine HIV screening in healthcare settings. Feasibility studies have demonstrated that screening is effective in high-volume, urban settings, but there are no data for smaller, more rural settings. The main objective of this study was to describe a routine HIV screening program at a community health center in South Carolina serving both urban and rural populations. Margaret J. Weston Community Health Center implemented routine HIV screening using rapid tests at its three locations on December 1, 2006. All individuals utilizing this center over the age of 13 years were screened for HIV unless they opted out. Nurses completed a survey about their experiences with the program. chi(2) tests and logistic regression models were used to analyze the data. In the first 8 months, among 985 eligible visits, 574 (58%) resulted in the patient being screened. The most common reason for refusal was "doesn't think s/he is at risk." Acceptance rates differed significantly by location (p = 0.01), from 62% in the urban site to 47% in the rural site. Other significant predictors of accepting HIV testing were race/ethnicity, age, and method of payment. Three hundred twenty-four (58%) individuals who were tested reported no history of being previously tested for HIV infection. Participation in the screening program was perceived favorably by nurses. This pilot project in a South Carolina community health center demonstrates that implementation of routine HIV screening is acceptable in small healthcare settings and in smaller cities and rural communities in the South.