Threats to subject retention in a controlled clinical trial require strategies that encourage continued participation of subjects, with consideration of the effect of the strategies on the dependent variable. Methods to encourage retention must be based on sensitivity to the patient's changing condition and perspective. Primary considerations in the design and implementation of an intervention study are the acceptability of the intervention to particular patients and the compatibility of the intervention with other care activities. In addition, qualities of the research personnel and changes in patient conditions are important factors in retention of subjects. Vignettes illustrate the threats to retention and solutions used in a clinical trial. Threats to retention include the research nurse's approach and patient factors such as worries, control issues, visitors, symptoms of confusion and pain, and lack of cooperation. Retention strategies include supporting and educating research nurses, providing empathy and respect, including patients in decisions, negotiating with visitors, alleviating symptoms, and supporting a plan of care consistent with both the research protocol and the patient's recovery. While providing a similar approach to all groups, experimental researchers in a variable clinical environment must also provide some individualization and communication to retain valuable subjects who are ill.