We have observed oscillations of intracellular Ca2+ (Ca[i]) concentration in populations of ras-transfected HaCaT keratinocytes of I-7 subline. In postconfluent monolayers of I-7 keratinocytes, an increase in extracellular Ca2+ (Ca[o]) concentration to 0.25-0.5 mM induced sinusoidal Ca(i) oscillations, which persisted longer than 1 h with amplitudes of 50-150 nM and periods of 5-10 min. Thapsigargin, which depletes internal Ca2+ stores, did not prevent Ca(o)-induced Ca(i) oscillations, and it also induced Ca(i) oscillations in the ras-transfected I-7 line. Removal of extracellular Ca2+ or addition of Ca2+-entry blocker La3+ or SK&F 96365 inhibited Ca(i) oscillations, suggesting that Ca(i) oscillations in ras-transfected HaCaT keratinocytes were dependent on Ca2+ influx across the plasma membrane. Because the Ca(o)-induced Ca(i) oscillations have been observed only in ras-transfected I-7 subline and not in its nontransfected parental HaCaT line, this may provide a partial explanation for the divergent responses of ras-transfected and nontransfected keratinocytes to Ca(o) signal for control of growth and differentiation.