Venous distensibility, i.e. Δ volume/Δ pressure, was examined in vivo in humans and in vitro in canine veins. Saline and isoproterenol (1 and 3 μg) when injected directly into the venous segment examined had no effect on the distensibility of superficial forearm veins. Aminophylline on the other hand (48 and 100 mg) significantly increased distensibility, as did dihydroxypropyl-theophylline. Similar results were obtained when 480 mg aminophylline was injected into a distant vein. The venous distensibility of dogs in vitro was not significantly changed either by isoproterenol or aminophylline. Drugs may alter venous distensibility, and this should be considered in their pharmacological and therapeutic evaluation.