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 intracellular free Ca++ concentration ([Ca++]i) responses evoked by bradykinin and thapsigargin in gingival fibroblasts. Tenidap itself stimulated [Ca++]i response in a dose-dependent manner in the absence of extracellular Ca++. The pretreatment with tenidap inhibited [Ca++]i responses evoked by 5 nM bradykinin and 1 microM thapsigargin in a dose-dependent manner. This indicates that tenidap discharges intracellular Ca++ store, resulting in a depletion of intracellular Ca++ store. Tenidap partially depressed Ca++ influx across plasma membrane by 1 to 2 min pretreatment and almost completely by more than 5 min pretreatment. Thus, tenidap appears to be a valuable agent that functions on inhibition of Ca++ influx in nonexcitable cells, which is rare at the present time.