The effect of tenidap [(+/-)-5-chloro-2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-oxo-1H-indole-1-carboxamide], a new anti-inflammatory agent, was investigated on DNA synthesis by means of [(3)H]thymidine incorporation, collagen synthesis by means of [(3)H]proline incorporation, cell proliferation, and intracellular pH in nicardipine-reactive human gingival fibroblasts. Tenidap significantly inhibited [(3)H]thymidine incorporation at concentrations greater than 20 microM on the 4th and 8th day of treatment. Tenidap also significantly inhibited [(3)H]proline incorporation at a concentration greater than 50 microM on the 4th day and at more than 20 microM on the 8th day of treatment. The presence of 1 microM nifedipine or 1 microM nicardipine did not alter the depressing effect of tenidap. Tenidap (20 microM) also lowered intracellular pH. These results suggest that tenidap might be effective for the prevention of gingival overgrowth caused by calcium channel blockers.