Retinoic acid and the protein kinase C inhibitor staurosporine have been reported to inhibit the invasiveness of tumor cells and may potentially be used to prevent metastatic disease. We report that retinoic acid reduced the invasiveness of 6 of 6 ras-transformed rat fibroblast cell lines and that inhibition did not require expression of the c-Jun component of AP-1. In contrast, staurosporine reduced the invasiveness of only 1 of 4 ras-transformed cell lines. The effect of staurosporine on the invasiveness of human tumor cell lines varied with cell type and length of treatment. We conclude that retinoic acid, but not necessarily staurosporine, decreases the invasiveness of ras-transformed fibroblasts.