1. Pretranslational suppression of glucose transport protein, isozyme 4 (GLUT 4), is a major mechanism of insulin resistance in adipocytes in obesity and non-insulin-dependent diabetes mellitus (NIDDM). 2. Patients with gestational diabetes mellitus (GDM) are heterogeneous; adipocyte GLUT 4 levels are either normal or markedly reduced but all patients exhibit abnormalities in GLUT 4 subcellular distribution and insulin-mediated translocation. 3. Skeletal muscle GLUT 4 expression is normal in obesity, impaired glucose tolerance (IGT), GDM, and NIDDM, indicating that functional activity or translocation of GLUT 4 may be impaired. 4. Adipocyte defects in GDM consistent with abnormalities in GLUT 4-vesicle traffic have implications with respect to potential mechanisms of insulin resistance in human muscle. Given the central role of insulin resistance in NIDDM and Syndrome 'X', elucidating the underlying mechanism in muscle is critical for developing more effective treatment and disease prevention.