This study examines dihydropyridine receptor (DHPR) gene expression in mouse skeletal muscles during physiological adaptations to disuse. Disuse was produced by three in vivo models -- denervation, tenotomy and immobilization, and DHPR _1s mRNA was measured by quantitative Northern Blot. After 14 days simultaneous denervation of the soleus (SOL), tibialis anterior (TA), extensor digitorum longus (EDL), and gastrocnemius (GASTR) by sciatic nerve section, DHPR mRNA increased preferentially in the SOL and TA (+1.6 fold); whereas, it increased in the EDL (+1.6 fold) and TA (+1.8 fold) after their selective denervation by peroneal nerve section. It declined in all muscles (-1.3 to -2.6 fold) after 14 days tenotomy, which preserves nerve input but removes mechanical tension. Atrophy was comparable in the denervated and tenotomized muscles. These results suggest that factor(s) in addition to inactivity per se, muscle phenotype, or associated atrophy can regulate DHPR gene expression. To test the contribution of passive tension to this regulation, we subjected the same muscles to disuse by limb immobilization in a maximally dorsi-flexed position. DHPR _1s mRNA increased in the stretched muscles (SOL, +2.3 fold; GASTR, +1.5 fold), and decreased in the shortened muscles (TA, -1.4 fold; EDL, -1.3 fold). The effect of stretch was confirmed in vitro. DHPR protein did not change significantly after 4d immobilization, suggesting that additional levels of regulation may exist. These results demonstrate that DHPR _1s gene expression is regulated as an integral part of the adaptive response of both slow and fast skeletal muscles to disuse, and identify passive tension as an important signal for its regulation in vivo.