To evaluate the efficacy of cytidine diphosphoryl choline (CDP-choline) in treating postconcussional symptoms for one month after mild to moderate closed head injury (CHI), we completed a preliminary double blind placebo-controlled study. Fourteen young men admitted to the neurosurgery service after sustaining mild to moderate CHI were randomized to oral CDP-choline (1 g) and placebo control groups which were matched for age, education and severity of impaired consciousness. Baseline (prior to discharge) and one month examinations consisted of a structured postconcussional symptom interview and neuropsychological tests. Results (Wilcoxon test) showed that CDP-choline produced a greater reduction of postconcussional symptoms than placebo (P less than 0.005). Analysis of the neuropsychological findings revealed a significantly greater improvement in recognition memory for designs in the CDP-choline treated patients (P less than 0.02) whereas other changes in test performance did not differ for the two groups. Pending replication in a larger series of patients, our findings suggest that CDP-choline may be effective in treating sequelae of mild to moderate CHI.