To date, relatively little progress has been made in the treatment of spinal cord injury (SCI)-related neurological impairments. Until now, methylprednisolone (MP) is the only agent with clinically proven beneficial effect on functional outcome after SCI. Although the mechanism of action is not completely clear, experimental data point to protection against membrane peroxidation and edema reduction. The melanocortin melanotropin is known to improve axonal regeneration following sciatic nerve injury, and to stimulate corticospinal outgrowth after partial spinal cord transection. Recently, we showed that intrathecally administered alphaMSH had beneficial effects on functional recovery after experimental SCI. Since both drugs have shown their value in intervention studies after (experimental) spinal cord injury (ESCI), we decided to study the effects of combined treatment. Our results again showed that alphaMSH enhances functional recovery after ESCI in the rat and that MP, although not affecting functional recovery adversely by itself, abolished the effects observed with alphaMSH when combined. Our data, thus, suggest that the mechanism of action of MP interferes with that of alphaMSH.