Site-specific sociodemographic recruitment, retention, and compliance (RRC) data were solicited at two points in time from the 18 National Institutes of Health-funded Community Programs for Clinical Research on AIDS (CPCRA). Based on their experiences delivering primary care to human immunodeficiency virus-infected individuals, nurses at each site identified organizational and client-centered factors functioning as barriers to protocol participation. In addition, the clinicians described the nature, frequency, and relative success of strategies used to enhance recruitment, retention, and protocol compliance. CPCRA units where nurses had clearly identified RRC barriers related to protocol design also were the sites that had accrued the most research participants. This study suggests that as the CPCRA units evolve, the most successful programs will be those in which the clinical and research staff can identify and develop innovative strategies that will successfully overcome RRC barriers.