This paper describes the background in experiment and theory on which present-day studies of the biochemistry of learning and memory are based. It then reviews specifically the use of passive avoidance training in the day-old chick as a model for the analysis of the cellular events associated with memory-formation. It shows how training chicks on this simple one-trial task can produce a coordinated series of short and long-term changes in specific regions of the chick forebrain, notably the left intermediate hyperstriatum ventrale (IMHV). In this region, shortly after training there are transient changes in the phosphorylation of a presynaptic 52 kDa protein, a protein kinase C substrate believed to be identical with B50. Longer-term changes include enhanced synthesis of protein, and in particular, synaptic membrane fucoglycoproteins. Experiments are described which demonstrate that the synthesis of these fucoglycoproteins is directly associated with memory storage and that inhibitors of synthesis prevent long-term memory formation. Other, morphological experiments show that following training and in association with memory formation there is an increase in the numbers of dendritic spines and an enlargement of spine head diameter in projection neurons of the IMHV. It is proposed that the increased fucoglycoprotein synthesis is part of the biochemical housekeeping process involved in the increased spine production and associated synaptic remodelling which represents the cerebral memory trace.