The Marshfield Epidemiologic Study Area (MESA), a geographically defined population registry at one of the participating sites in SUPPORT (a multicenter study of the care of seriously ill hospitalized patients) permitted assessment of generalizability in that study. On the basis of age- and sex-specific rates of enrollment of SUPPORT patients in MESA, we estimate that about 400,000 patients per year would fulfill SUPPORT eligibility criteria in the United States. However, an estimated 925,000 patients, particularly the elderly and those with impairments in their activities of daily living (ADLs), have SUPPORT-like illnesses annually, but do not receive the aggressive care required for study enrollment. The absence of patients not interested in aggressive care in tertiary care-based studies is compounded by the overrepresentation of patients referred from distant areas to the tertiary care center. Such patients tended to be older and to have different diseases than patients in MESA. Care should be taken in generalizing results from clinical and epidemiologic studies conducted at tertiary care centers.