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The significant increase of serum cortisol concentration associated with involuntary manual or mechanical restraint during venipuncture was absent in females who were trained to voluntarily cooperate during the procedure in the homecage. The present findings indicate that training rhesus monkeys to cooperate during in-home-cage venipuncture is a simple way to increase the validity of research data because it helps to avoid undue excitation and associated alteration in basal physiology of the research subjects.