Percutaneous needle biopsy samples were obtained from the vastus lateralis and soleus muscles before and after 30 d of 6 degree head-down bedrest to determine the influence of this model of simulated microgravity on human skeletal muscle. Fiber atrophy was evident in both muscles with both fast-twitch and slow-twitch fiber cross-sectional areas decreasing. Predominant atrophy of slow-twitch fibers was not evident. The soleus had a greater proportion of slow-twitch fibers than the vastus lateralis before bedrest. Neither muscle showed a change in fiber type percentage with bedrest. Phosphofructokinase and lactate dehydrogenase activities in the soleus and vastus lateralis muscles were similar before and after bedrest. The activities of beta-hydroxyacyl-CoA dehydrogenase and citrate synthase, however, were reduced during bedrest with these responses being somewhat greater in the soleus. While the ultrastructure of most of the fibers of the soleus and vastus lateralis appeared normal after bedrest, evidence of remodeling was present in both muscles. The proliferation of core/targetoid lesions, honeycomb networks, regenerating satellite cells, necrotic foci and myofibrillar disorganization after bedrest indicates that force development is an important factor in determining the organization of the fine structure of muscle. The results indicate that short-duration exposure to simulated microgravity decreases fiber size and the capacity for aerobic energy supply of human skeletal muscle. Moreover, disorganization of the contractile machinery occurs. Thus, it appears that bedrest alters the "normal" load-time constraints imposed on skeletal muscle sufficiently to change its inherent structural and metabolic characteristics.