This study examined the effect of stationary ground support (2 and 4 h/day) and uphill running (1.5 h/day, 20 m/min, 30% grade) activity patterns on soleus muscle atrophy and slow myosin loss during 4 wk of rodent hindlimb unweighting by tail suspension. We also examined the effect of uphill running during the last 4 wk of an 8-wk hindlimb unweighting program and during 4 wk of cage recovery after 4 wk of hindlimb unweighting. All forms of activity partially spared soleus muscle weight (mg), myofibril protein (mg/muscle pair and microgram/mg muscle), and relative and absolute slow myosin (SM) isoform content (% of total and mg/muscle pair, P less than 0.05). Relative to the normal control soleus muscle, the uphill running regimens resulted in 1) increased fast myosin isoform content and 2) diminished recovery of SM isoform content when coupled with cage activity recovery. Four weeks of cage recovery after 4 wk of hindlimb unweighting resulted in recovery of the relative SM isoform content to proportions exceeding normal control values, suggesting an apparent degradation of any normally existing fast myosin. These results indicate that, in the context of the hindlimb unweighting model, the mechanisms controlling the expression of soleus muscle SM and fast myosin genes can be affected differently by the diverse activities of stationary ground support, unrestricted cage activity, and programmed uphill running.