Basing his medical system on the recent discovery of the circulation of the blood by the English anatomist William Harvey, while keeping it within the general framework of the classic Greek physician Galen's humoral theories, Sylvius felt that the most important processes of normal and pathological life take place in the blood and that diseases (human disease) should be explained and treated chemically. Recognizing the existence of salts in living matter, he concluded that they were the result of an interaction of acids and bases; thus, he postulated that chemical imbalances consist of either an excess of acid (acidosis) or an excess of alkali (alkalosis) in the blood, and he devised drugs to counteract these conditions.

A professor of medicine at the University of Leiden (1658–72), Sylvius was one of Europe's outstanding teachers. He was among the first to introduce ward instruction in medical education, and he instigated the construction of perhaps the first university chemistry laboratory. He was the first to distinguish between two kinds of glands: conglomerate (made up of a number of smaller units, the excretory ducts of which combine to form ducts of progressively higher order) and conglobate (forming a rounded mass, or clump). He also discovered (1641) the deep cleft (Sylvian fissure) separating the temporal (lower), frontal, and parietal (top rear) lobes of the brain.