In animals, oxytocin enhances maternal behavior and lowers blood pressure (BP) and negative affect, while parturitional cocaine disrupts oxytocin activity and increases maternal neglect and aggression. Thus, we compared oxytocin, BP, maternal behavior, and affect in mothers of infants who used cocaine (cocaine, n = 10) or did not (no drug, n = 25) during pregnancy. Laboratory BP and circulating oxytocin, catecholamines, and cortisol were examined before and during a speech stressor on 2 days, with vs. without prestress baby holding. Ambulatory monitoring assessed BP, urinary norepinephrine, and cortisol for 24 h at home. The cocaine group had lower oxytocin levels, greater hostility and depressed mood, less support from others and mastery over life events, higher BP during all events of testing without the baby, and higher ambulatory BP and urinary norepinephrine at home, while cortisol and epinephrine responses were blunted. Although they tended to hold their babies less often at home, baby holding in the laboratory led to decreased BP in cocaine mothers who then did not differ from no-drug mothers in BP or observed affect.