To determine the appropriateness and effectiveness of medical interventions, it is necessary to understand both the natural history of the conditions the interventions are intended to treat or prevent, and the normal reference ranges of tests used in diagnosis and management. The acquisition of this information through clinic-based studies can yield misleading conclusions owing to selection bias. What appears to be intervention-related variation in outcomes may be variation in the magnitude and form of selection bias. To minimize selection bias, population-based studies are required. Results from the Olmsted County Study of Urinary Symptoms and Health Status Among Men were used to show how a population-based longitudinal study of the natural history of benign prostatic hyperplasia (BPH) can complement research programs of the BPH Patient Outcomes Research Team. Population-based studies of disease natural history are a necessary part of medical outcomes research, and deserve greater emphasis in the medical treatment effectiveness research initiative of the Agency for Health Care Policy and Research.