A14-125I-monoiodoinsulin binding to, internalization into, and degradation inside human circulating monocytes, a cell type widely used for insulin receptor studied, from normal(32) and weight, age-matched NIDDM(31) subject were studied. The specific insulin binding, internalization and degradation were decreased in the cells from NIDDM compared to that in the cells from normal subjects. Scatchard plot analysis of these group data reveal that cells from the normal control subject contain 28,000 receptor sites per cell, while monocytes from the NIDDM patients contain 15,000 sites per cell. These results indicate that the decreased abilities of insulin binding, internalization and degradation of target cells may play a role in the cellular resistance to insulin that occurs in the NIDDM.