Two types of calcium (Ca²⁺) signaling-propagating intercellular Ca²⁺ waves of increasing intracellular Ca²⁺ concentration ([Ca²⁺]_i) and nonpropagating oscillations in [Ca²⁺]_i-co-exist in a variety of cell types. To investigate this difference in Ca²⁺ signaling, airway epithelial cells were loaded with heparin, an inositol 1,4,5-trisphosphate (IP₃) receptor antagonist, by pulsed, high-frequency electroporation. Heparin inhibited propagation of intercellular Ca²⁺ waves but not oscillations of [Ca²⁺]_i. In heparin-free cells, Ca²⁺ waves propagated through cells displaying [Ca²⁺]_i oscillations. Depletion of intracellular Ca²⁺ pools with the Ca²⁺-pump inhibitor thapsigargin also inhibited the propagation of Ca²⁺ waves. These studies demonstrate that the release of Ca²⁺ by IP₃ is necessary for the propagation of intercellular Ca²⁺ waves and suggest that IP₃ moves through gap junctions to communicate intercellular Ca²⁺ waves.