The purpose of this study was to investigate the contribution of calcineurin-related intracellular signal for heat-stress-associated muscle hypertrophy. Wistar strain male rats (7-week-old) were randomly divided into four groups: (1) control (CC, n=15), (2) control with the injection of cyclosporine A (CsA) (CA, n=15), (3) heat-stressed (HC, n=15), and (4) heat-stressed with the injection of CsA (HA, n=15). The heat-stress groups (HC and HA) were exposed to heat (41 degrees C for 60 min) in a controlled heat chamber without anesthesia. Soleus and extensor digitorum longus (EDL) muscles were dissected and weighed 1, 7, and 14 days after the exposure. Wet and dry weights of soleus were increased 7 days following heat exposure. The expressions of heat shock protein 72 (HSP72) and calcineurin in both muscles were also increased within 1 and 7 days following heat-stress, respectively. Administration of CsA, a specific inhibitor for calcineurin, depressed heat-stress-associated increase of muscle weight and calcineurin expression, especially in soleus. These observations suggest that a calcineurin-dependent signaling pathway may play an important role in the heat-stress-related skeletal muscular hypertrophy. Application of heat-stress to skeletal muscles may be a useful tool to gain muscular mass and force generation not only in athletes, but also in patients during rehabilitation.