As a part of a continuing study on the healing of flexor tendons, the effects of an antihistamine–antiserotonin compound (promethazine) were studied in 109 chickens. A form of standard surgical trauma to the intact flexor profundus tendon was devised, and the results of several different methods of administration of promethazine were compared. These studies indicate that minimal surgical trauma applied to an intact flexor tendon produces a marked reaction consisting of a degenerative phase, a phase of dedifferentiation, and a phase of regeneration and maturation. The histological studies reveal that such highly specialized intercellular substances as collagenic fibers and bundles, though non-living, are not inert and permanent structures. They can break down, completely disappear, and be reformed as a result of the reaction to trauma of specialized tenocytes and undifferentiated mesenchymal cells of the tendon and epitenon. The effects of an antihistamine (promethazine) are to prolong the phase of degeneration and loss of differentiation and, upon withdrawal, to accelerate the phase of growth and maturation. These effects vary with the dose and method of administration of promethazine.