Following 10 days of daily restraint stress, sensitization developed to the stimulatory effect of amphetamine on locomotion in DBA/2 but not in C57BL/6 mice tested 24 h after the last stressful experience regardless of their being naive or habituated to the test cages. Saline-injected C57BL/6 mice, however, showed an increase of locomotion 24 h after chronic stress treatment. Chronically stressed mice of the two strains did not exhibit any alteration of dopamine and metabolites (3-4-dihydroxphenylacetic acid, homovanillic acid, and 3-methoxytyramine) levels in the frontal cortex, caudatus putamen, or nucleus accumbens septi, thus ruling out that stress-induced alteration of basal dopamine metabolism affected the behavioral response to amphetamine challenging in DBA/2 mice. Ten daily amphetamine injections (5 mg/kg) did not significantly modify the behavioral response to amphetamine in either strain of mice tested 24 h after the end of the chronic treatment and did not increase locomotion in saline-injected C57BL/6 mice. Finally, chronically stressed hybrids B6D2F1 did not show sensitization to the locomotor effects of amphetamine, suggesting a dominant mode of inheritance in the response to chronic stress of the C57BL/6 strain.