Intermittent repetitive mechanical stimulation of differentiated avian skeletal muscle cells in vitro for 48 h stimulates skeletal muscle growth [Am. J. Physiol. 256 (Cell Physiol. 25): C674-C682, 1989]. During the first 2-3 h of stimulation, temporary muscle damage occurs based on increases in creatine kinase efflux, total protein degradation rates, and several proteinase activites. With continued mechanical stimulation for several days in serum-containing medium, the proteinase activities return to control levels, and total protein degradation rates decrease to levels less than static controls. Decreased protein degradation thus contributes to stretch-induced cell growth. The efflux of prostaglandins (PG) E2 and F2 alpha but not 6-keto-PGF1 alpha increase with mechanical stimulation. During the first 5 h of stimulation, PGE2 and PGF2 alpha efflux rates increase 101 and 41%, respectively. PGE2 efflux returns to control levels by 24 h of mechanical stimulation, whereas PGF2 alpha efflux is continuously elevated (41-116%) for at least 48 h. The long-term stretch-induced elevation of PGF2 alpha efflux correlates with a 52-98% long-term increase in total protein synthesis rates. The prostaglandin synthesis inhibitor indomethacin partially blocks early stretch-induced cell damage and long-term stretch-induced cell growth. The results indicate that both of these processes are partially dependent on stretch-induced increases in prostaglandin synthesis.