Differential screening of a cDNA library derived from mRNA of TGF beta-treated serum-free mouse embryo (astrocyte precursor) cells isolated a strongly TGF beta-regulated mRNA that codes for cystatin C, a cysteine protease inhibitor. Increase in cystatin C mRNA level was observed within four hours after treatment with picomolar concentrations of TGF beta. The increase was reversible upon removal of TGF beta and was not prevented by cycloheximide. These results suggest that cystatin C expression may represent a developmentally regulated differentiated function of astrocytes, and also suggest that cystatin C expression may be involved in the response of brain cells to platelet release of TGF beta after trauma or injury.