Calcium antagonists are the gold standard in the therapy of coronary heart disease and hypertension. The prototype of these drugs is nifedipine which, as well as its therapeutic effects on the cells of the cardiovascular system, also has unpleasant side effects on other organ systems. One side effect can be a missive hyperplasia of the gingiva, the reason for which are unclear. In vitro experiments were designed to elucidate the influence of nifedipine on the growth of human gingival fibroblasts in short and long term (72 hours, 6 weeks) cell culture. The following cellular parameters were determined quantitatively: cell proliferation (cell count, [3H]thymidine incorporation), protein synthesis ([3H]glucosamine incorporation) and viability (release of lactate dehydrogenase). A significant increase in cell proliferation (up to 1 microgram/ml nifedipine) was observed in the short-term experiments (72 hours, 0.001-10 micrograms/ml nifedipine), no other parameters were altered or were even depressed at higher concentrations. A significant increase in the cell proliferation and a decrease in the proteoglycan synthesis was found in the long term experiments (6 weeks, 1 microgram/ml nifedipine). Our results indicate that nifedipine has a direct effect on the cell proliferation of the gingival fibroblast in cell culture. The effect of nifedipine on the gingival fibroblasts are therefore similar to those observed earlier by the widely used immunosuppressant drug cyclosporin A on human gingival fibroblast in culture.