Objective: The aim of our investigation was to study the mechanism responsible for the predominant expression of fast-type myosin heavy chain IId (MHC IId) in a previously described primary muscle cell culture. Methods: Skeletal muscle cells from newborn rabbits are cultivated on gelatin microcarriers in suspension under continuous rotary motion of the cell culture medium. This rotary motion of the medium, in which the myotube-carrier-aggregates are suspended, exerts mechanical forces on the myotubes that form bridges between carriers. After 14 days in culture an adult myosin expression pattern is reached and we either continue the exposure to the passive mechanical forces or we stop the rotary motion for 2 - 6 days. Results: Passive mechanical forces induce significant increases in MHC IId, IGF-1 (insulin-like growth factor-1) and MGF (mechano growth factor) RT-PCR products, Western Blot-detected MHC II protein and total protein per cell. No changes are found in MHC I, IGF-1 receptor, GAPDH (glyceraldehyde-3-phosphate dehydrogenase), fumarase and PGC-1 (peroxisome proliferator-activated receptor gcoactivator 1a) RT-PCR products. Furthermore, Western Blots show that passive mechanical forces reduce the activity of Akt (PKB), Erk1/2 (p44/p42 MAPK) and SAPK/JNK but increase the activity of p38 MAPK. We find that the activation of p38 MAPK and the increase of IGF-1 RT-PCR products seen under passive mechanical forces are suppressed by the integrin inhibitor echistatin (25 nM). Conclusions: We conclude that passive mechanical forces are sensed by integrin, which transduces the mechanical signal into activation of p38 MAPK. Activation of p38 MAPK has been shown previously to lead to selective upregulation of MHC IId. The direct link between passive forces and expression of MHC IId constitutes a novel mechanism, which is expected to be effective under physiological conditions of passive stretch and eccentric contractions of skeletal muscle.