Modified muscle use can result in muscle atrophy and impairment. We tested whether inflammatory cell concentrations correlate temporally with muscle impairment during modified loading periods. Rat hindlimbs were unloaded for 10 days followed by reloading. The density of neutrophils and ED1+ macrophages was significantly increased by 16.5- and 9.8-fold, respectively, after 1 day of reloading. ED2+macrophage concentration was not significantly increased until 3 days of reloading. Maximal isometric tetanic tension (Po; N/cm2) decreased during hindlimb suspension (HS), which was followed by a second drop in Poafter 2 h of reloading. This latter loss in muscle force was uncoupled with the significant elevation in muscle inflammatory cell concentrations. Experiments where HS soleus muscles were incubated with caffeine revealed that at least 40% of the Po decrement at 2 h could be associated with a loss of efficiency of the excitation-contraction (E-C) coupling process. These data suggest that an important mechanism for the early loss in force is the inability to activate the contractile machinery likely caused by a failure in the E-C coupling process during the reloading period.