Vesalius had corrected the structure of the body; but how it worked was still understood according to Galen's model from the second century. For Galen the liver continually produced new blood from food, this blood moved back and forth in the body like a tide and was consumed in the tissues; blood was assumed to seep between the two sides of the heart through invisible pores.

The English physician William Harvey (1578–1657) tested this model with a scientist's most powerful tool — measurement. He estimated the amount of blood the heart pumps with each beat and multiplied by the pulse rate: the result implied that the body produced many times its own weight in blood every hour, which was impossible. The only reasonable explanation was that the same blood circulated again and again.

He made this concrete with experiments. Tying off an arm, he showed how the veins swelled; he demonstrated that the small valves in the veins let blood pass only toward the heart, preventing backflow. The heart was a suction-and-force pump; blood left through the arteries and returned through the veins, circulating continuously in a closed circuit. His slim 1628 book "De Motu Cordis" (On the Motion of the Heart) laid out this proof.

Harvey could not see the capillaries joining arteries to veins — Malpighi would find them under the microscope only decades later; but he predicted their existence by logic. "De Motu Cordis" is the founding text of experimental physiology, where observation and quantitative reasoning overturned authority. Medicine was beginning to listen not to the ancient text but to the measured body.