BC3H1 and C2C12, murine cell lines, were assessed as model systems for the expression of ryanodine receptor protein during myogenesis. The ryanodine receptor is a calcium release channel of the sarcoplasmic reticulum and a component of the triad junction, a structure which is essential to excitation-contraction coupling in mature striated muscle. BC3H1 and C2C12 cells do not express the ryanodine receptor at detectable levels in a proliferative, nondifferentiated state. The ryanodine receptor protein is expressed during differentiation in BC3H1 and C2C12 cells, becoming detectable within 24 hr of the onset of differentiation. In both cell lines the ryanodine receptor is assembled in oligomeric form and binds [3H]ryanodine with high affinity. Fusion is not required for expression of the ryanodine receptor in either BC3H1 or nonfusing C2C12 cells. The level of expression of the ryanodine receptor protein is modulated by incubation with the growth factors TGF-beta and bFGF in a manner similar to that of other muscle-specific proteins. These initial observations suggest that the BC3H1 and C2C12 cell lines provide a model system for further investigations of the expression and function of the ryanodine receptor during myogenic differentiation.