Day-old chicks trained on a single trial passive avoidance learning task showed a significant increase, relative to untrained controls, in activity of the Ca2+/calmodulin-dependent protein kinase (CaMK) in the particulate fraction from tissues from the intermediate medial hyperstriatum ventrale region of the forebrain. The increased kinase activity was observed within 10 min following training and persisted for at least 70 min posttraining. Amnesia for the task was induced by micromolar concentrations of the specific CAMK II antagonist, KN-62, administered into the neostriatal/hyperstriatal region of the forebrain. The effect of KN-62 was lateralized. In the right hemisphere, KN-62 induced amnesia only when injected within 2. 5 min following training, with memory loss evident by 5 min posttraining. In contrast, in the left hemisphere amnesia was induced by KN-62 administered as late as 5 min posttraining, with onset of amnesia occurring after 10 min posttraining. The findings were interpreted within the context of a three-stage model of memory formation.