Muscle and muscle-derived collagens largely form the developing intestinal wall. Transforming growth factor-beta (TGF-β1) exerts potent effects on muscle cell proliferation and collagen deposition. Mechanical forces regulate cell behavior in conjunction with growth factors and local matrix. Intestinal smooth muscle undergoes brief rhythmic stretch during peristalsis and persistent stretch proximal to obstruction. Objective: to determine the effects of both intermittent and persistent stretch on α1(I) collagen and TGF-β1 expression in developing human intestinal smooth muscle cells. Methods: Primary cultures of muscle cells at 20 weeks gestation were plated onto circular silicone membranes. Confluent cultures were subjected to either a short period of cyclical mechanical distention, or distended tonically for 18 hours. Unstretched cultures served as controls. Collagen and TGF-β1 mRNA abundance was determined by Northern blot analysis, quantitated by phosphorimaging and normalized to 18S ribosomal RNA. Results: Intermittent mechanical distention resulted in a 70% increase in mRNA content of TGF-β1 in comparison to unstretched controls, but no change in mRNA content of α1(I) collagen. Persistent mechanical distention resulted in a 3.4 fold increase in mRNA content of TGF-β1 and a 9.2 fold increase in mRNA content of α1(I) collagen in comparison to controls. Summary: Mechanical stretch modulates muscle expression ofα1(I)collagen and TGF-β1 mRNAs. Persistent stretch markedly enhances expression. Conclusion: Stretch alters the expression of the major structural collagen and a key growth factor found in developing intestinal muscle. The degree and nature of that stretch may in part regulate subsequent development of the muscle wall.