Treatment with glucocorticoids causes wasting of proximal skeletal muscles. The purpose of the present investigation was to quantify in the thigh muscle the areas of the different fiber types determined by histochemical methods, and the muscle ultrastructure by means of electron microscopy, in normal subjects (N = 41) and in renal transplant patients treated with prednisone (N = 12). The cross-sectional area of all three fiber types was reduced in renal transplant patients treated with prednisone (10.6 +/- 4.3 mg/day), the fast glycolytic fibers being most affected (slow oxidative fibers: 2642 +/- 625 vs. 3677 +/- 970 micron2, P less than 0.001; fast oxidative fibers: 3275 +/- 735 vs. 4443 +/- 1343 micron2, P less than 0.01; fast glycolytic fibers: 2305 +/- 802 vs. 3920 +/- 1522 micron2, P less than 0.001). This was mostly due to a decrease in the volume of myofibrils per unit volume of muscle fiber (-30%). The intracellular lipid content and the volume density of subsarcolemmal mitochondria were increased by more than 70% in prednisone treated patients. In conclusion, the decreased myofibril areas might account for the muscle weakness in renal transplant patients treated with prednisone, and the decrease in myofibrils is in part functionally compensated by an increase in subsarcolemmal mitochondria and intracellular lipid content.