Effects of locally elevated shear stresses on thoracic histamine formation and transmural albumin uptake have been examined under in vivo conditions in anesthetized male, mongrel dogs. Results indicate that if endothelium remains intact, significant linear relationships exist between the shear intensity and aortic histamine-forming capacity and aortic content of fluorescein-labeled bovine serum albumin following 20 h of circulation time. These data suggest that in vivo the aortic (and endothelial) histidine decarboxylase system is sensitive to local alterations in applied shear stress, and that de novo aortic histamine synthesis in involved in mediating shear-induced increases in aortic transmural permeability.