Abstract The purpose of this study was to describe the factors that homeless persons report as influencing their decisions to utilize or reject a public health disease-detection program. Although there is copious literature on homelessness, few studies report the real-life perspectives of homeless persons toward health or health promotion. A convenience sample of 55 sheltered and street-dwelling homeless persons, who either resided in or were visiting seven shelters in a large northeastern U.S. city, were interviewed. The interview questions focused on the bases for decisions to accept or reject tuberculosis screening. The in-depth semistructured audio-taped interviews were transcribed, coded, and categorized using Ethnograph software. Interviews were analyzed using the constant comparative content analysis methods. The findings describe homeless persons' reasons for accepting or rejecting a tuberculosis-detection service, the prominent role of shelter personnel in recruitment for health-related interventions, and the confidentiality needs of women with children. This information can assist community health practitioners in designing and advertising health-promotion and disease-detection programming.