The present experiment examined the effects of sex and gonadectomy on cocaine-induced locomotor activity via intravenous (IV) cocaine. Male, female, castrated (CAST), and ovariectomized (OVX) rats received daily IV cocaine injections (3.0 mg/kg/injection) for 13 consecutive days. Locomotor activity was measured in automated activity chambers for 60 min following the baseline-saline administration and after the 1st and 13th cocaine injections. Observational time sampling was also performed, and the observational data were grouped into locomotor and orofacial composite incidence scores. Females exhibited more cocaine-induced locomotor activity, rearing, and locomotor incidence compared to males. The orofacial data revealed a sex difference in the expression of behavioral sensitization: females exhibited more orofacial behaviors than males after repeated, but not acute, cocaine injection. Females exhibited more cocaine-induced locomotor activity, rearing, and locomotor incidence compared to OVX rats, but exhibited less orofacial incidence following acute cocaine administration. There were no differences between male and CAST rats. CAST rats showed more locomotor incidence than OVX after repeated, but not acute, cocaine injection. CAST rats exhibited behavioral sensitization, whereas OVX rats' locomotor incidence did not change with repeated cocaine injection. CAST rats showed less orofacial incidence than OVX after acute, but not repeated, cocaine injection. These findings demonstrate sex differences in response to IV cocaine and replicate earlier findings which show that OVX attenuates increased locomotor activity in females. Furthermore, these findings suggest that IV cocaine administration produces behavioral differences between male and female rats in the absence of circulating gonadal hormones.