Results of numerous experimental studies support the notion that antibiotic inhibitors which disrupt brain RNA or protein synthesis can selectively block the formation of long-term memory for various tasks in several species 1-3,5,12,1a. There is, however, little evidence to suggest whether one can anatomically localize the site of the amnesic effect of these agents. While Flexner et al. 9 compared the effects of injection of puromycin into frontal, temporal and ventricular regions of mouse brain on Y-maze retention, subsequent reports suggested that the resulting amnesia in mice may be unrelated to the effect of the drug on protein synthesis 10. Consolidation, as evidenced by a rapidly growing insusceptibility of memory to subcutaneous or intracerebral injections of antibiotica, 4, was not observed in Flexner's experiments. Subcutaneous injection of another protein synthesis inhibitor, cycloheximide, results in profound inhibition of protein synthesis throughout the body, including the brain, and is accompanied by amnesia 3. The parenteral injection does not permit demonstration of putative brain regions that might mediate the amnesic effect. We recently demonstrated by means of radioautography that a zone of inhibition can be demarcated following stereotaxic intracerebral injection of small volumes of either puromycin or cycloheximide in the monkey v. The present report summarizes experimental results which suggest localization of the effects of small stereotaxically injected doses of cycloheximide (CXM) on protein synthesis and memory in the mouse. Eight-week-old female CD-1 mice (Charles River) were housed individually 3 days before one-trial step-through passive avoidance training. Apparatus and training procedures were based on a procedure reported by Flood et al. s. A subject was placed into the small compartment of a two-chamber test box. After a 1 rain habituation period, a sliding door separating the two chambers was opened, allowing the mouse to enter the large shock chamber. Five seconds after entry, the door was closed and a 0.15 mA scrambled shock was delivered through the grid floor. After a 2 sec * Present address: Dept. of Psychology, Massachusetts Institute of Technology, Cambridge, Mass., U.S.A. ** To whom communications should be sent.