Syndecan‐4 and its cytoplasmic binding partner, synectin, are known to play a role in FGF‐2 signaling and vascular growth. To determine their roles in coronary artery/arteriolar formation and growth, we compared syndecan‐4 and synectin null mice with their wild‐type counterparts. Image analysis of arterioles visualized by smooth muscle α‐actin immunostaining revealed that synectin ^−/− mice had lower arteriolar length and volume densities than wild‐type mice. As shown by electron microscopic analysis, arterioles from the two did not differ in morphology, including their endothelial cell junctions, and the organization and distribution of smooth muscle. Using micro‐computer tomography, we found that the size and branching patterns of coronary arteries (diameters > 50 μm) were similar for the two groups, a finding that indicates that the growth of arteries is not influenced by a loss of synectin. Syndecan‐4 null male mice also had lower arteriolar length densities than their gender wild‐type controls. However, female syndecan‐4 null mice were characterized by higher arteriolar length and volume densities than their gender‐matched wild‐type controls. Thus, we conclude that both synectin and syndecan‐4 play a role in arteriolar development, a finding that is consistent with previous evidence that FGF‐2 plays a role in coronary arterial growth. Moreover, our data reveal that gender influences the arteriolar growth response to syndecan‐4 but not to synectin. Developmental Dynamics 236:2004–2010, 2007. © 2007 Wiley‐Liss, Inc.