This investigation utilized gross dissections, histological preparations, and neurophysiologic experiments to gain an improved understanding of the innervation of the human knee. Anatomical illustrations represent the findings of dissections of 15 fresh amputation specimens. Neurohistologic preparations using silver staining techniques demonstrate the rich innervation of the soft tissues of the knee, and a variety of specialized receptors are identified. In 10 subjects with normal knees, and experimentally produced knee effusion of 60 cc was found to result in profound inhibition of reflexly evoked quadriceps contraction. Clinical implications of the anatomical and physiologic data are discussed.