This paper discusses sampling and design considerations relevant to the estimation of exposure to organochlorine compounds in epidemiological studies. We consider exposures measured directly via biomarkers of exposure in the body. It is critical for the design, implementation, and evaluation of studies that epidemiologists and biostatisticians be familiar with methodological issues relevant to the direct measure of exposure. Etiologic, toxicokinetic, quality control and quality assurance, and statistical sampling are discussed. Finally, the limitations of these studies and the need for complete reporting of methods are discussed.