I review here key research in the early years of the field of blood chemistry. The review includes successes and limitations of animal chemistry in the critical period of the eighteenth and nineteenth centuries. Eighteenth century medical theories emphasized the primacy of body solids. Body fluids were governed by the tenets of humoral pathology. After Boerhaave sparked interest in the chemistry of the body fluids, a new humoralism developed. With the rise of animal chemistry in the eighteenth century, two complementary ideas came into play. The concept of vital force was introduced in 1774, and the chemical composition of animal matters, including the blood, began to be investigated. In the early nineteenth century, the development of new methods of analysis encouraged such chemical studies. Prominent chemists led the field, and physicians also became involved. Physiologists were often opposed to the chemical tradition, but François Magendie recognized the importance of chemistry in physiology. Liebig linked the formation and functions of the blood to general metabolism and so extended the scope of animal chemistry from 1842. About the same time, microscopic studies led to discoveries of the globular structure of the blood, and Magendie's famous pupil, Claude Bernard, began the animal chemistry studies that led him to new discoveries in hematology. This review addresses discoveries, controversies, and errors that relate to the foundations of clinical chemistry and hematology and describes contributions of instrumental investigators.