We have tested the effects of exogenous proteases on the growth of normal and transformed hamster fibroblasts in the classic culture assays for transformation. The results indicate that exogenous proteases act to decrease the serum requirement of normal cells but not nearly to the extent that occurs in the process of viral transformation. Proteases do not further decrease the serum requirement of transformed cells, nor do they affect the maximal saturation density or the plating efficiency in soft agar of either normal or transformed cells. Under conditions optimal for growth stimulation, proteases decrease the strength of cell-to-substrate adhesion but do not affect cellular morphology. In contrast to previous studies, experiments using highly purified trypsin and several different active-site inhibitors strongly suggest that the growth-stimulatory activity of trypsin is not directly related to the proteolytic activity of the molecule.