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General protease and collagenase IV activity are involved in the remodelling of the vascular basement membrane that occurs during tumor-induced angiogenesis. This study has assessed the level of these enzymes in tumor, peritumoral or contralateral cerebral cortex tissue during the growth of C6 astrocytoma in the rat spheroid implantation model. General proteolytic activity was increased in tumor tissue beginning on day 8 following spheroid implantation, then increased to a maximum value on day 11 and decreased to control values on day 18. A similar pattern was seen for collagenase IV activity but maximal activity occurred on day 13. The peritumor and tumor patterns of activity were similar. General protease activity was increased in the hemisphere contralateral to the tumor suggesting that the growth of C6 astrocytoma in rat brain was influencing biochemical events distant from the tumor. C6 astrocytoma cells orchestrate a cascade of proteolytic events which may play a crucial role in angiogenesis associated with tumor growth in the model system studied.