Tension is an important regulator of skeletal muscle hypertrophy in vivo. When increased constant tension is applied to embryonic skeletal muscle fibers differentiated in a tissue culture environment, many of the same biochemical processes associated with muscle hypertrophy in vivo are also stimulated in vitro, e.g., sodium-dependent amino acid transport, Na+,K+-ATPase (sodium pump) activity, protein synthesis, total protein, and myosin heavy chain accumulation. The molecular mechanisms by which tension induces these growth-related changes are unknown, but several models have been tested using whole animal, organ-cultured muscle, and tissue culture model systems. In tissue culture, activation of the plasma membrane sodium pump is closely coupled to, and essential for, stretch and serum-induced skeletal muscle growth. Long-term membrane hyperpolarization is not associated with this sodium pump activation, and muscle growth in vitro is unrelated to the myotube's resting membrane potential, since growth can occur under de-polarizating conditions. Medium growth factors are essential for stretch-induced muscle growth in tissue culture. In medium without growth factor supplements, stretch is able to reduce the rate of atrophy of the cultured muscle cells which are in negative nitrogen balance, but the muscle cells are unable to grow in response to stretch without the presence of some as yet undefined growth factor or factors present in serum. As newer tissue culture environments are designed for growing embryonic skeletal muscle under more in vivo-like conditions, a more complete analysis of the mechanisms by which a physical stimulus (tension) is translated into the biochemical alterations leading to muscle growth will be possible.(ABSTRACT TRUNCATED AT 250 WORDS)