The primary objective of this study was to compare the magnitude of injury in mouse extensor digitorum longus (EDL) and soleus muscles induced by high-force eccentric contractions. A second objective was to study the effect of altering the daily loading of the muscles through hindlimb suspension (HS) on the injury. One of two protocols was performed in vitro: 1) 15 eccentric contractions (n = 20: 10 EDL and 10 soleus muscles) or 2) 15 isometric contractions (n = 20: 10 EDL and 10 soleus muscles). After the protocol, the decrements in contractile performance and lactate dehydrogenase (LDH) release were measured at 15-min intervals over 1 h. Immediately after the eccentric contraction protocol, markedly greater decrements in maximal isometric tetanic force (Po) occurred in the normal EDL than in the normal soleus muscles (60.7 +/- 4.2 vs. 7.6 +/- 2.1%, P < or = 0.0001). LDH release immediately after the eccentric contraction protocol was 2.7-fold greater in the normal EDL than in the normal soleus muscles. To investigate the role of recent loading of the muscles in the injury, EDL (n = 9) and soleus (n = 10) muscles from mice subjected to HS for 14 days performed the eccentric contraction protocol. HS resulted in greater decrements in contractile performance for the soleus muscles (decreases in Po immediately after the protocol for HS and normal soleus muscles were 31.0 +/- 1.8 and 7.6 +/- 2.1%, respectively; P < or = 0.0001) but not for the EDL muscles.(ABSTRACT TRUNCATED AT 250 WORDS)