SYNOPSIS. The sarcoplasmic reticulum is the intracellular membrane system in skeletal muscle fibers which regulates the Ca2$ concentration of the myofibril and thereby the contraction relaxation cycle. In the past the proposed explanation for the differences in the contractile properties of fast and slow skeletal fibers has been attributed mainly to quantitative rather than qualitative differences in the structure, function and molecular composition of the sarcoplasmic reticulum of these two fiber types. Recent immunocytochemical and biochemical studies have, however, clearly demonstrated that the Ca2$-ATPase of the sarcoplasmic reticulum in slow skeletal fibers is structurally and thus perhaps also functionally related to that of the cardiac fibers, but distinctly different from that of fast skeletal fibers. Furthermore similar studies have shown that phospholamban, a cardiac sarcoplasmic reticulum protein believed to modulate the activity of the cardiac Ca2$-ATPase, is also present in slow but not fast skeletal fibers. The availability of antibodies specific to the fast and slow isoforms of the Ca2$-ATPase, and to phospholamban will now enable us to apply immunocytochemical labeling techniques to examine the effect of neuronal and other physiological signals on the regulation of the gene expression of sarcoplasmic reticulum proteins at the cellular level.