Summary Synapses in the rat dentate gyrus are rapidly lost after removal of the primary input from the entorhinal cortex. In this paper we describe the extent and time course of degeneration and in the subsequent paper the nature of the reinnervation process. The synapses of entorhinal afferents are remarkably concentrated in their zone of termination. Unilateral removal of the rat entorhinal cortex results in the loss of about 86% of all synapses in the outer three-fourths of the molecular layer of the ipsilateral dentate gyrus. Entorhinal synapses are all asymmetric (Gray type I) and terminate on dendritic spines. Analysis of the degeneration reaction provides a means to examine the characteristics of the loss of a relatively homogeneous afferent on a single cell type. The morphological characteristics of the degenerating terminals showed some heterogeneity; both the electron lucent and electron dense types of degenerating termimals were identified. The electron lucent type was observed only at short survival times. The time course of the loss of degenerating terminals was resolvable into two components, each of which followed first order decay kinetics. Thus degenerating entorhinal terminals behaved as a population which disappeared randomly at a rate dependent on the fraction of terminals present at any time. The loss of degenerating terminals was accompanied by the loss of the postsynaptic sites. At short survival times the majority of postsynaptic sites (defined by the presence of a postsynaptic density) had disappeared. There was also a loss of complex spines and some shrinkage of the molecular layer.