This study tested the hypothesis that elevation of heat stress proteins by whole body hyperthermia is associated with a decrease in skeletal muscle atrophy induced by reduced contractile activity (i.e. , hindlimb unweighting). Female adult rats (6 mo old) were assigned to one of four experimental groups (n = 10/group): 1) sedentary control (Con), 2) heat stress (Heat), 3) hindlimb unweighting (HLU), or 4) heat stress before hindlimb unweighting (Heat+HLU). Animals in the Heat and Heat+HLU groups were exposed to 60 min of hyperthermia (colonic temperature approximately 41.6 degrees C). Six hours after heat stress, both the HLU and Heat+HLU groups were subjected to hindlimb unweighting for 8 days. After hindlimb unweighting, the animals were anesthetized, and the soleus muscles were removed, weighed, and analyzed for protein content and the relative levels of heat shock protein 72 (HSP72). Compared with control and HLU animals, the relative content of HSP72 in the soleus muscle was significantly elevated (P < 0.05) in both the Heat and Heat+HLU animals. Although hindlimb unweighting resulted in muscle atrophy in both the HLU and Heat+HLU animals, the loss of muscle weight and protein content was significantly less (P < 0.05) in the Heat+HLU animals. These data demonstrate that heat stress before hindlimb unweighting can reduce the rate of disuse muscle atrophy. We postulate that HSP70 and/or other stress proteins play a role in the control of muscle atrophy induced by reduced contractile activity.