Neurons of the central ganglia of opisthobranch and pulmonate gastropods increase in size as the animals grow, some becoming veritable giants. The origins and functions of neuronal giantism are considered here from a comparative viewpoint. A review of the properties of identified neurons in a variety of opisthobranch and pulmonate species indicates that neuronal size is directly related to the extent of postsynaptic innervation. DNA endoreplication, resulting in partial or complete polyploidy, supports giantism in molluscan neurons as it does in eukaryotic cells elsewhere. Apparently, the functional significance of giantism is enhanced synthesis and transport of materials to serve an expanded presynaptic function. Giant neurons are found in larger snails where they innervate large areas of the periphery; interneurons and sensory neurons are enlarged to a lesser degree, probably to that which enables load-matching to the peripheral effectors. Neuronal giantism may be an adaptation for the innervation of the periphery in large animals with simple behaviors and uncomplex sensoria, this adaptation enabling growth of body and CNS without a proportionate increase in neuronal number. A more complete understanding of the evolutionary and adaptive significance of neuronal giantism should be sought in comparative studies of the cellular properties of simple and complex molluscan brains.