What is blood? Despite William Harvey’s discovery of the circulation of blood, many questions about blood itself remained unanswered. This article asks how and why Dutch medical men in the early eighteenth century initiated studies to understand the properties of blood. Medical professors analysed blood in chemical laboratories, as they believed that blood chemistry promoted new understandings of human physiology and pathology. Others, however, grew to be deeply sceptical about chemistry and argued that there existed a discrepancy between blood in vitro and blood in vivo. They preferred quantitative measurements, hoping that these would provide useful knowledge for making diagnoses and treating wounds. This article analyses these competing approaches to blood research, arguing that the discussion went beyond the problem of methodology and was directly linked to the question of blood’s essential yet disputed quality: was blood alive?