Rhesus monkeys (Macaca mulatta) were trained to perform a foot lever pressing task for a food reward. EMG activity was recorded from selected lower limb muscles of 2 animals before, during, and after a 14-day spaceflight and from 3 animals during a ground-based simulation of the flight. Integrated EMG activity was calculated for each muscle during the 20-min test. Comparisons were made between data recorded before any experimental manipulations and during flight or flight simulation. Spaceflight reduced soleus (Sol) activity to 25% of preflight levels, whereas it was reduced to 50% of control in the flight simulation. During flight, medial gastrocnemius (MG) activity was reduced to 25% of preflight activity, whereas the simulation group showed normal activity levels throughout all tests. The change in MG activity was apparent in the first inflight recording, suggesting that some effect of microgravity on MG activity was immediate.