Previous research has shown that magnesium chloride (MgCl(2)) and riboflavin (B(2)) both significantly improve functional recovery when administered shortly after frontal cortical contusion injury (CCI). The purpose of the present study was to examine the ability of combination treatments of MgCl(2) and B(2) to improve functional outcome following unilateral CCI. One hour post-injury, rats were administered MgCl(2) (1.0 mmol/kg), B(2) (7.5mg/kg), MgCl(2)+B(2) (1 mmol/kg+7.5mg/kg), 1/2 MgCl(2)+1/2 B(2) (0.5 mmol/kg and 3.75 mg/kg), or saline. Two days following CCI rats were tested on a battery of sensorimotor (vibrissae-->forelimb placing and tactile removal test) and motor (staircase test). A regimen of MgCl(2)+B(2) significantly reduced the initial impairment and facilitated the rate of recovery on the tactile removal test and facilitated the rate of recovery on the forelimb placing test. The half-dose combination did not significantly improve functional recovery on the tactile removal test compared to the individual treatments; however, it did improve performance on the forelimb placing test compared to saline treatment. Administration of MgCl(2) improved performance on the placing and tactile removal tests on 2 post-operative days, as did treatment with B(2) on the tactile removal test. The results indicate that the full combination of MgCl(2)+B(2) significantly improved functional recovery to a greater extent than the individual treatments or the low dose combination group on forelimb placing but not on tactile removal. These findings suggest that administration of MgCl(2)+B(2) may provide better therapeutic action than individual treatments.