We studied the reasons surgical principal investigators chose not to enter patients in a large, multicenter trial sponsored by a cooperative group. In 1976 the National Surgical Adjuvant Project for Breast and Bowel Cancers (NSABP) initiated a clinical trial to compare segmental mastectomy and postoperative radiation, or segmental mastectomy alone, with total mastectomy. Because the low rates of accrual were threatening to close the trial prematurely, we mailed a questionnaire to the 94 NSABP principal investigators, asking why they were not entering eligible patients in the trial. A response rate of 97 per cent was achieved. Physicians who did not enter all eligible patients offered the following explanations: (1) concern that the doctor-patient relationship would be affected by a randomized clinical trial (73 per cent), (2) difficulty with informed consent (38 per cent), (3) dislike of open discussions involving uncertainty (22 per cent), (4) perceived conflict between the roles of scientist and clinician (18 per cent), (5) practical difficulties in following procedures (9 per cent), and (6) feelings of personal responsibility if the treatments were found to be unequal (8 per cent). Further investigation into the behavioral aspects of the investigator-patient relationship is particularly pressing, since fear of change in this relationship was the most common reason given for not entering eligible patients in the trial.