Although the rising incidence of breast cancer has prompted a surge of intervention strategies aimed at increasing women's use of mammography screening, the majority of patient-directed interventions have not been driven by relevant theoretical work on persuasive health communication. The authors evaluated an intervention derived from prospect theory that was designed to increase women's adherence to recommendations for annual mammography screening. They sent 1 of 3 reminder letters (positive frame, negative frame, or standard hospital prompt) to 929 randomly selected women who were due for mammography screening and had been identified as having either a positive or negative family history of breast cancer. The primary hypothesis that women with a positive history would be more responsive to negatively framed messages, whereas women with a negative history would be more responsive to positively framed letters, was not confirmed. The lack of support for predictions derived from prospect theory raises important questions about the generalizability of laboratory research to natural settings.