We studied the effective spread of lidocaine to inactivate neural tissue in the frontal cortex of the rhesus monkey. Injections of 2% lidocaine at 4 microl/min were made while units were recorded 1 or 2 mm away. To inactivate units 1 mm away from the injection site 100% of the time, 7 microl of lidocaine had to be injected. To inactivate units 2 mm away from the injection site 100% of the time, 30 microl of lidocaine were required. Units were maximally inactivated around 8 min after the start of a lidocaine injection, and they gradually recovered, regaining most of their initial activity by around 30 min after the start of an injection. The volume of lidocaine required to inactivate neurons > 90% of the time could be estimated by the spherical volume equation, V = 4/3 pi (r)3. To prolong the inactivation, a slower infusion of lidocaine subsequent to an initial bolus was effective. Saline control injections had no effect. These results allow both a prediction of the timecourse of neural inactivation and an estimate of the spread of neural inactivation following injection of lidocaine into the monkey cerebral cortex.