Cyclosporine-A (CsA) has been increasingly used as an immunosuppressant concomitant with neural transplantation treatment for different degenerative disorders. However, the possible role that CsA itself may have in the recovery of transplant patients is not known. Some investigators have argued that clinical improvement following transplantation (e.g., myoblast) may be confounded by CsA administration. The present study was conducted to delineate CsA-induced behavioral alterations. Four groups of normal 5-wk old Sprague-Dawley rats (n = 8 per group) were utilized in two separate experiments. In both experiments, two groups of animals were used; each group either received daily injections of 15 mg/kg of CsA or olive oil for 32 days (experiment 1) and 21 days (experiment 2). Animals in both experiments were subsequently tested for nocturnal locomotor behavior. Animals in experiment 2 were further tested in passive avoidance task, motor coordination, and amphetamine-induced locomotor activity. Results demonstrated that CsA-treated animals were significantly hyperactive compared to controls across the 12-h nocturnal activity periods and in amphetamine-induced locomotor activity. No significant differences between the CsA- and vehicle-treated animals were observed in passive avoidance or in motor coordination. Postmortem analyses of dopamine and its metabolites in the striatum and olfactory tubercle did not show any significant differences between the CsA- and the vehicle-treated groups. In summary, CsA significantly increased nocturnal spontaneous and amphetamine-induced locomotor behavior, but the neurochemical correlates for these effects need to be investigated. In addition, while the present study demonstrated that CsA induced motor alterations, any possible effects CsA may have on neurological or dystrophic patients with motor dysfunctions remain to be determined.