Stress is a risk factor in drug addiction, enhancing development and increasing relapse. However its role during development has received little attention. This study will investigate if social isolation during early development alters the behavioral response to cocaine. Pregnant Sprague Dawley rats were housed 1 (prenatal isolation group) or 2 (control group) rats per cage. From postnatal day 2‐9, pups from the neonatal isolation group were isolated for 60 min in a separated cage. At day 21 (weaning), pups from the postnatal isolation group were housed individually. Another group was isolated during both prenatal and postnatal period. Control rats were maintained with dam and siblings and at weaning, housed 4‐5/cage of the same sex. At day 22, and for 5 consecutive days, pups were injected daily with saline or cocaine (15 mg/kg/i.p.) followed by 7 drug free days. A challenge injection of saline or cocaine (15 mg/kg,i.p.) was given on day 13. Locomotor activity was recorded on days 1, 5, and 13. Only rats that were isolated during both prenatal and postnatal period showed an increase in cocaine‐induced behavioral sensitization as compared to control rats. These data indicate that isolation stress during perinatal development enhances the behavioral response to drugs of adolescent rats. [Support contributed by NIH grants: U54NS39405 (SNRP); SO6‐GM08224 (MBRS/SCORE)]