Remifentanil and propofol infusions were used to provide neuroleptanalgesia during an awake craniotomy to resect a left frontoparietal glioblastoma near the motor speech center. This operation presented anesthetic requirements ranging from adequate analgesia during bone flap removal to an appropriate level of consciousness during cortical speech mapping. We performed pharmacokinetic simulations to estimate the effect site concentrations of propofol and remifentanil as the infusion rates were modulated to meet the dynamic sedation and analgesic needs of the operation. Simulations revealed that changes in infusion rates were quickly followed by changes in the effect site concentrations which corresponded well with the desired changes in patient sedation and analgesia. We propose that remifentanil and propofol in combination may be a useful technique for awake craniotomy.