The inter-relationship of the bacteria, vegetations and cardiovasculature was studied by light and electron microscopy in experimental staphylococcal endocarditis and aortitis in acute and fatal infections. A specific spatial relationship was observed with the majority of bacterial colonies located along the junction between the cardiovasculature and the overlying thrombic vegetation. The bacterial colonies within the vegetations on the ventricular and aortic walls were smaller and embedded in a thick layer of thrombus with certain colonies showing evidence of bacterial cell death. By comparison, the lesions on the aortic valve consisted of large masses of bacteria with little or no thrombic coating. The structural damage to the aortic valve appeared to be the direct result of bacterial invasion into the connective tissue of the cusp. The acute nature of the disease may be related to bacterial destruction of the aortic valve whereas the colonies within the aortic wall vegetations are probably the source of 'resistance' to antibiotic treatment.