The primary reinforcing effect of morphine was compared in two genetically inbred strains of mice (C57BL/6 and DBA/2) using the intravenous self-administration procedure in drug naive animals. The morphine self-administration differed between the mouse strains. DBA/2 but not C57BL/6 acquired self-administration of morphine with a bell-shaped unit dose-response curve. Acute physical stress induced by electrical footshocks did not significantly affect the self-administration in both strains. Acute emotional stress induced by forcing mice to witness another mouse being subjected to acute physical stress caused a shift of the bell-shaped unit dose-response curve of morphine self-administration to the left in the DBA/2 mice. The C57BL/6 mice, which initially failed to demonstrate stable self-administration, started to self-administer morphine after emotional but not physical stress. Emotional distress may increase the individual sensitivity to the rewarding effects of morphine and may render an individual more susceptible to development of drug dependence.