Femoral and abdominal adipose tissue cellularity and metabolism as well as muscle morphology and metabolism were examined in women with Cushing's syndrome and compared with those in nonobese women and obese women with the android and gynoid types of fat distribution. Cushing's syndrome was characterized by abdominal obesity and enlarged abdominal fat cells, with adipose tissue lipoprotein lipase activity elevated 2-3 times that in normal women and low lipolytic capacity. Muscle tissue in women with Cushing's syndrome had a relatively low proportion of type I (30%) and a high proportion of type IIB (32%) muscle fibers, similar to those in android obesity (45% and 25%, respectively) and in contrast to fiber composition in gynoid obesity (55% and 12%, respectively). Glycogen synthase activity in the lateral vastus muscle was very low. We suggest that the enlargement of abdominal fat depots in women with Cushing's syndrome is at least partially due to elevated adipocyte lipoprotein lipase activity and low lipolytic activity. Furthermore, the abnormal muscle fiber composition might be caused by the corticosteroid excess. Such muscle is known to be relatively insulin insensitive and might thus contribute to the marked insulin resistance that occurs during chronic corticosteroid excess.