Open biopsy of adipose tissue from volunteer subjects has led to a greater understanding of the mechanisms of adipose-tissue insulin resistance in various clinical states. Studies of adipose tissue obtained during surgical operations have allowed development of techniques and exploration of adipocyte physiology. This has been particularly valuable in examining the relationship between cellular insulin binding and action. Examination of the lipid stores and of enzyme activities has been possible by using the more convenient technique of needle biopsy. Regional differences in adipose tissue metabolism have been identified and must be considered in experimental design. It is now clear that the insulin sensitivity of any one metabolic pathway does not necessarily reflect that of others, and care must be taken to avoid inappropriate extrapolation of data both between metabolic pathways in the adipocyte itself and from the adipocyte to the whole body.