Maternal deprivation for 24 hr is known to produce hyperactivity in 2-week-old infant rats kept at nest temperature. Pretreatment with reserpine (0.5 mg/kg), at the time of separation, prevented the development of hyperactivity over the ensuing 24-hr, whereas the same dose in mothered littermates had no residual effects on behavior the next day. d-Amphetamine (0.25 and 2.0 mg/kg) produced dose-dependent increases in locomotion and rearing and decreases in self-grooming behavior, which were of comparable magnitude whether the pups were separated and kept warm, normally mothered, or separated at room temperature, a condition known to produce decreased activity levels. Cardiac rates were not affected by either drug; reserpine lowered respiratory rates slightly, amphetamine increased body temperature following behavior testing. Altered accumulation of catecholamines at presynaptic terminals is discussed as a possible neurochemical mechanism for behavior changes following maternal separation in this model system.