Hindlimb unweighting is a commonly used model to study skeletal muscle atrophy associated with disuse and exposure to microgravity. However, a discrepancy in findings between single fibers and whole muscle has been observed. In unweighted solei, specific tension deficits are greater in whole muscle than in single fibers. Also, metabolic enzyme activity when normalized per gram of mass is depressed in whole muscle but not in single fibers. These observations suggest that soleus muscle interstitial fluid volume may be elevated with atrophy caused by unweighting in rats. The purpose of this study was to determine if soleus muscle atrophy induced by unweighting is accompanied by alterations in muscle interstitial fluid volume and to calculate the effect of any such alterations on the muscle specific tension (N/cm2 muscle cross-sectional area). Nine female Wistar rats (200 g) were hindlimb unweighted (HU) by tail suspension. Soleus muscles were studied after 28 days and compared with those from five age-matched control (C) rats. Interstitial fluid volume ([3H]inulin space) and maximum tetanic tension (Po) were measured in vitro at 25 degrees C. Soleus muscles atrophied 58% because of unweighting (C = 147.8 +/- 2.3 mg; HU = 62.3 +/- 3.6 mg, P less than 0.001). Relative muscle interstitial fluid volume increased 107% in HU rats (35.5 +/- 2.8 microliters/100 mg wet mass) compared with the control value of 17.2 +/- 0.5 microliters/100 mg (P less than 0.001); however, absolute interstitial fluid volume (microliters) was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)