Neurons display a variety of complex dendritic morphologies even within the same class. We examined the relationship between dendritic arborization and the coupling between somatic and dendritic action potential (AP) initiation sites in layer 5 (L5) neocortical pyramidal neurons. Coupling was defined as the relative reduction in threshold for initiation of a dendritic calcium AP due to a coincident back-propagating AP. Simulations based on reconstructions of biocytin-filled cells showed that addition of oblique branches of the main apical dendrite in close proximity to the soma (d < 140 microm) increases the coupling between the apical and axosomatic AP initiation zones, whereas incorporation of distal branches decreases coupling. Experimental studies on L5 pyramids in acute brain slices revealed a highly significant (n = 28, r = 0.63, P < 0.0005) correlation: increasing the fraction of proximal oblique dendrites (d < 140 microm), e.g., from 30 to 60% resulted on average in an increase of the coupling from approximately 35% to almost 60%. We conclude that variation in dendritic arborization may be a key determinant of variability in coupling (49 +/- 17%; range 19-83%; n = 37) and is likely to outweigh the contribution made by variations in active membrane properties. Thus coincidence detection of inputs arriving from different cortical layers is strongly regulated by differences in dendritic arborization.