Protein kinase C (PKC) activators, such as phorbol-12-myristate- 13-acetate (PMA), are well known to induce increased synthesis of procollagenase along with cell rounding in fibroblasts. Calcium channel blockers, such as verapamil, and calmodulin inhibitors, like trifluoperazine, are known to induce alteration of fibroblast cell shape (from multipolar to spherical). This morphological change is probably caused by the depolymerization of actin filaments. When fibroblasts recover from calcium antagonist mediated cytomorphological changes, they increase synthesis of procollagenase. Calcium antagonists exert these effects in both normal human dermal fibroblasts (AG07095) and keloid fibroblasts (CB792, CW792 and WT949). Protein kinase C inhibitors (such as tamoxifen and H-7) also induce cell rounding, depolymerize actin filaments and increase procollagenase synthesis in human skin fibroblasts. Tamoxifen effectiveness in treating desmoid and other fibrotic tumors may be due to its ability to promote extracellular matrix degradation by increasing procollagenase synthesis. The depolymerization of actin filaments by calcium channel blockers, calmodulin inhibitors or protein kinase C inhibitors is probably the result of an increase in the cytosolic calcium ion concentration caused by calcium release from internal storage sites. Protein kinase C plays an important role in the induction of cell rounding because protein kinase C activator (SC-9) inhibits calcium antagonist-induced cell rounding. The results of this thesis clearly demonstrate that PKC inhibition also leads to cytomorphological responses and increases procollagenase synthesis. The precise biochemical pathway for this response is unknown. However, some evidence for a inositol-1.4.5-triphosphate (IP3) mediated pathway is presented.