The striatum, the main component of the basal ganglia, is composed of mainly one type of neuron, the so-called medium spiny neuron. This neuron cell type, which constitutes over 90% of striatal neurons, is the major output neuron of the striatum. Combined ultrastructural neuroanatomical methods have elucidated the organization of afferent connectivity to these neurons. The major physiologic function of striatal efferent activity appears to be inhibition of tonically active GABAergic neurons in the globus pallidus and substantia nigra pars reticulata. Thus, the excitatory input from the cerebral cortex, whose afferents make asymmetric synapses with the spines of medium spiny neurons, appears to drive the efferent activity of the striatum. Other extrinsic and intrinsic afferent synapses are situated in a position to regulate the effect of the corticostriatal excitatory input to the medium spiny neurons. For example, dopaminergic afferents from the midbrain make mainly symmetric synapses with the spine necks and dendritic shafts of the medium spiny neurons. Medium spiny neurons themselves have local axon collaterals, in addition to their efferent axon that exits the striatum, which serve to link together local clusters of medium spiny neurons. These local axon collaterals, which contain either GABA, substance P, or enkephalin, also make mainly symmetric synapses with the necks of spines or dendritic shafts of medium spiny neurons. Other afferents with similar synaptic connections to these neurons arise from cholinergic or somatostatinergic striatal intrinsic neurons. Additionally, the patterns of extrinsic and intrinsic afferents to medium spiny neurons and their extrinsic projections are related to the organization of medium spiny neurons into two mosaically organized macroscopic compartments, the striatal patches and matrix.