Our previous study indicated that fibroblasts derived from patients reactive to nifedipine might be susceptible to the other calcium-channel blockers (nicardipine, verapamil and diltiazem) in terms of cell proliferation, DNA synthesis, and collagen synthesis. Thus, the present investigation was designed to clarify the cross-reactivity among dihydropyridine calcium-channel blockers (nifedipine, nicardipine, and nisoldipine). Human gingival fibroblasts derived from seven, two, and one patients who developed gingival overgrowth as a result of nifedipine, nicardipine, and nisoldipine medications, respectively, were examined in terms of the effect of calcium-channel blockers (nifedipine, diltiazem, verapamil, and nicardipine) on cell proliferation, DNA synthesis, collagen synthesis, and the number of epidermal growth factor (EGF) receptors. Phenytoin was used as a positive control. With most of the calcium-channel blockers and phenytoin, fibroblasts from patients reactive to nifedipine and nicardipine medications gave a better cell proliferation rate, DNA synthesis, and an increased number of EGF receptors, compared to non-drug-treated control. However, this was not the case for calcium-channel blockers tested in fibroblasts from patients reactive to nisoldipine medication.