The Genetics Clinic is a collaborative undertaking by researchers from six institutes and the NIH Clinical Center. Consequently, clinic patients constitute a broad spectrum of genetic disease. The patient load during the clinic's fifth year comprised 471 individuals representing some 60 different diagnostic categories. Of these, 191 patients (40%) were seen by members of CEB. For our Branch, the Clinic provides a multidisciplinary setting in which to study unusual patients who either have cancer or an increased risk of developing malignancy. Patients are ascertained through special referrals from outside physicians and inhouse requests for etiologic consultations. With informed consent, the approach to the patient included detailed physical examination and, where applicable, epidemiologic studies of the environmental and genetic background and laboratory studies to clarify biologic mechanisms of carcinogenesis. Categories include patients with genetic diseases predisposing to malignancy, patients with birth defects and cancer, families with childhood sarcomas and breast cancer in blood relatives, and any other families with an excessive occurrence of cancer of any type.