We studied inositol-1,4,5-trisphosphate (IP(3)) receptor-dependent intracellular Ca(2+) waves in CA1 hippocampal and layer V medial prefrontal cortical pyramidal neurons using whole-cell patch-clamp recordings and Ca(2+) fluorescence imaging. We observed that Ca(2+) waves propagate in a saltatory manner through dendritic regions where increases in the intracellular concentration of Ca(2+) ([Ca(2+)](i)) were large and fast ('hot spots') separated by regions where increases in [Ca(2+)](i) were comparatively small and slow ('cold spots'). We also observed that Ca(2+) waves typically initiate in hot spots and terminate in cold spots, and that most hot spots, but few cold spots, are located at dendritic branch points. Using immunohistochemistry, we found that IP(3) receptors (IP(3)Rs) are distributed in clusters along pyramidal neuron dendrites and that the distribution of inter-cluster distances is nearly identical to the distribution of inter-hot spot distances. These findings support the hypothesis that the dendritic locations of Ca(2+) wave hot spots in general, and branch points in particular, are specially equipped for regenerative IP(3)R-dependent internal Ca(2+) release. Functionally, the observation that IP(3)R-dependent [Ca(2+)](i) rises are greater at branch points raises the possibility that this novel Ca(2+) signal may be important for the regulation of Ca(2+)-dependent processes in these locations. Futhermore, the observation that Ca(2+) waves tend to fail between hot spots raises the possibility that influences on Ca(2+) wave propagation may determine the degree of functional association between distinct Ca(2+)-sensitive dendritic domains.