Many studies suggest that protein synthesis is required for formation of long-term memory. To test whether the protein synthesis inhibitor anisomycin (ANI) actually inhibits long-term memory formation or whether apparent amnesia could be attributed to state-dependency, chicks were both trained and tested under the influence of anisomycin (ANI). Two-day-old cockerels were trained in a 1-trial passive avoidance task. Intracerebral injections (10 microliters per hemisphere) of either saline (SAL) or 11.0 mM ANI were made into the medial hyperstriatum ventrale 5 min pretraining and 5 min pretest. The ANI inhibited cerebral protein synthesis by 70-80%, a level necessary to cause amnesia. Chicks that pecked a small bead dipped in methylanthranilate (MeA) and were injected with SAL both pretraining and pretest avoided pecking at test, showing memory for the bitter substance; chicks given ANI pretraining and SAL pretest pecked at the bead during test, which suggests amnesia. However, those given ANI both pretraining and pretest showed marked avoidance at test. Chicks trained to peck at a small bead dipped in water and given injections of either SAL or ANI pretraining and SAL pretest pecked readily at test. However, water-trained chicks given ANI pretest, regardless of pretraining injection, showed significantly higher avoidance at test. We conclude that peck aversion in the ANI-MeA-ANI group was not due to state-dependency but to generalized avoidance induced by pretest ANI.