MM14 myoblasts, in contrast to their differentiation defective variant (DD-1) cells, do not synthesize detectable levels of prostaglandins or of the initial enzyme in the pathway of prostaglandin synthesis, prostaglandin H synthase (PGHS) but do exhibit readily detectable level of PGHS mRNA (Steiner, S., et al., 1991, Exp. Cell Res. 192, 643). These findings suggest a possible relationship between the myogenic phenotype and the synthesis of prostaglandins. This relationship was examined in the current study by analysis of the effect of transfection of DD-1 cells with a MyoD expression vector (termed MyoDD-1 cells) on expression of MyoD and synthesis of prostaglandins. Proliferating MyoDD-1 cells express readily detectable levels of MyoD protein and mRNA and exhibit markedly diminished levels of PGHS protein and prostaglandins. In contrast, serum-deprived MyoDD-1 cells express little MyoD mRNA or protein and exhibit a readily detectable level of PGHS protein despite having only a slightly higher PGHS mRNA abundance compared to growing MyoDD-1 cells. These studies are consistent with the hypothesis that MyoD expression contributes to the inhibition of prostaglandin synthesis.