Redistribution of lidocaine and bupivacaine was studied after intrathecal injection in mice qualitatively by whole-body autoradiography or quantitatively by determining spinal cord concentration of the drugs. The composition of the drug solutions then were changed to see if drug distribution could be altered. Changing thepH of the lidocaine solution from 7.5 to 5.0 by adding hydrochloric acid had no effect on spinal cord distribution. Simultaneous injection of bupivacaine and epinephrine increased the bupivacaine concentration in the spinal cord. By adding sucrose to a lidocaine solution, rostral spread of lidocaine was considerably less when the animals were restrained in a vertical position as compared with those injected with a plain solution. When lidocaine and bupivacaine were injected simultaneously, the spinal cord concentration was only changed to a small extent as compared with when the drugs were given separately. Whole body autoradiography revealed that both lidocaine and bupivacaine were rapidly redistributed rostrally from the lumbar area, but quantitatively the rostral redistribution is small. Whole body autoradiography also illustrated the elimination pathways from the spinal subarachnoid space. The authors conclude that alterations in the composition of the injected drug solution can affect rostral redistribution in the spinal cord tissue.