We assessed in 15 consecutive patients the best route and time of administration for phenytoin (PHT) prophylaxis in neurosurgical procedures. We also correlated PHT levels in serum and cerebrospinal fluid after oral and parenteral loading doses. The mean PHT level was 13.9 micrograms/ml in serum and 2.03 micrograms/ml in cerebrospinal fluid (CSF), with a significant correlation between levels in both compartments (r = 0.73, p < 0.01). Mean PHT levels among the different groups were not statistically significant. We conclude that therapeutic levels of PHT in CSF can be achieved independently of the route of administration, as long as accepted loading doses are used.