Specimens from 2 cases of gingival hyperplasia resulting from the treatment with the immunosuppressant cyclosporin A (CSGH) and 4 cases of inflamed gingiva (non-CSGH) were examined by electron microscopy with particular interest in the fibroblasts. In general, the fibroblasts in CSGH revealed the ultrastructural characteristics of active protein synthesis and secretion and less cytotoxic or degenerative changes. Some fibroblasts in the CSGH (23.8%) displayed cytological modifications comparable to so-called myofibroblasts, i.e., microfilament bands with semi-periodic dense nodes, nuclear indentations, and basal-lamina associated, cell-to-stromal junctions. Conversely, 5.9% of the fibroblasts in the non-CSGH showed these modifications. The modified fibroblasts were found most predominantly in the transitional area between inflamed and fibrous connective tissues. From these findings, it is suggested that the myofibroblastic modification in CSGH is regarded as a common morphological sign in actively proliferating fibrous tissue and may participate in the host-tissue response to the plaque-associated irritants.