Nifedipine induces overgrowth of gingival tissues in some patients. However, other collagenous tissues in their body do not overgrow. The purpose of this study was to compare effects of serial dilutions of nifedipine on the in vitro metabolism of fibroblasts derived from normal gingiva, nifedipine-induced hyperplastic gingiva, knee capsular ligament, and dermis. The data suggested that nifedipine affects the metabolism of fibroblasts derived not only from gingiva, but also from other collective connective tissues. Thus, nifedipine-responder cells are present in tissues other than gingiva. There was an inverse relationship between in vivo tissue levels of IL-1-beta and in vitro responsiveness to nifedipine of fibroblasts derived from that tissue. Nifedipine-induced overgrowth of connective tissues, other than gingiva, probably does not occur either because of the relatively slow rate of collagenous protein synthesis by resident fibroblasts or because of alterations in collagen deposition/resorption within susceptible tissues produced by nifedipine on collagenase synthesis.