In a survey on 26 clinical trials we have studied the reasons why some patients choose to participate in clinical trials while others decline. Interviews were held with 198 adult patients, just after they had been asked by the trial-clinician to participate. We interviewed patients who were asked to participate in a clinical trial, including those who decided not to participate. The theoretical guidelines to explain participation were based on an extended form of the Health Belief Model. Patients being asked to participate in a clinical trial decide by making a personal balance account. This comprises the physical and emotional added value patients hope to gain from the trial treatment compared to the non-trial treatment, minus the risks they expect in the trial and minus the extra time they expect the trial will take. The extent they feel physically threatened by their illness will also influence their decision. Furthermore, this personal balance account was found to depend on patient opinion about medical care and care-givers in general and on how patients regard their illness. Relatively long-term patients show a slightly different motivation to participate in a clinical trial than short-term patients. In line with the Health Belief Model, motivational beliefs on the relevance to reducing the threat to the patient's health condition ('values') and the evaluations of the clinical trial the patient is approached for ('expectancy'), are relevant in explaining patient behavior. Moreover, specific evaluative frames of reference are relevant in patients faced with the choice to participate or not. Suggestions are made to improve insight into patient motivation during the informed consent procedure of clinical trials.