Demand for measuring estradiol at low concentrations is increasing, and the widely used 'direct' radioimmunoassays that do not require a preliminary organic purification step may be inadequate in patient care because of their limited accuracy. In observational epidemiology, however, the main concern is to obtain a correct ranking of individuals' hormone concentration relative to the true level (as determined through a 'gold standard'). Despite differences in the absolute scale of measured and true concentrations, correct ranking will permit calculation of unbiased estimates of hormone-disease associations. In prospective studies, the major concerns are the limited volume of often irreplaceable specimens and the need to perform a large number of assays within a reasonable period of time. Organic purification is often not feasible because of sample volume requirements and logistic difficulties, and so the development of accurate, rapid and inexpensive methods to measure sex steroids at low concentrations would represent a valuable new research tool for both clinicians and epidemiologists.