AIM: To investigate the signal transduction mechanism of rapid effect of corticosterone. METHODS: With liquid scintillation technique, the effect of corticosterone on glycine uptake in C6 cells was examined. RESULTS: The bovine serum album in coupled with corticosterone had the same effect as corticosterone 21-sulfate(B); Neomycin partially blocked the effect of B in C6 cells; GDP-?-S attenuated the effects of B on glycine uptake in C6 cells; Chelerythrine chloride (Chelery) partially blocked the effect of B in C6 cells; H 89 had no influence on the effect of B in C6 cells. The Km and Vmax of effect of B on glycine uptake in C6 cells were different from those in SK-N-SH cells. CONCLUSION: PKC, instead of PKA, was involved in the signal transduction of the rapid effect of B on glycine uptake in C6 cells. The converse effects of B on C6 cells and SK-N-SH cells resulted from different transportation system in two kinds of cells.