At a given radiation dosage and field of view, five variables are under meaningful control for intravenous digital subtraction angiography (IV-DSA): concentration and quantity of contrast media injected, volume of injectate, rate of injection, and site of injection. Some controversy exists regarding the selection of a central vs. a peripheral injection site for IV-DSA. This study determined the influence of the site of injection on the peak and width of the arterial time-concentration curve produced by contrast media. Using a noninvasive, in vivo, quantitative x-ray measurement method, 36 separate injections (10 ml of ioxaglate at 8 ml/sec) were administered into the cephalic vein, subclavian vein, and main pulmonary artery in dogs. Injection sites were varied using a Latin-square experimental design. Cardiac output, central blood volume and the peak and width of the contrast media time-concentration curves were measured. The average peak enhancement was greatest for the pulmonary artery injection site. Normalizing peak and width values to make the pulmonary artery values 100%, the average peak values for injections into the subclavian vein and cephalic vein were 93% and 56%, and the average widths were 141% and 163%, respectively. These data support the use of a more central injection site for optimizing IV-DSA examinations.