Abstract Magnocellular neuroendocrine cells of the rat supraoptic nucleus undergo numerous morphological changes during chronic dehydration of the animal. These changes include increases in cell size, the percentage of neuronal membrane in direct apposition and formation of new multiple synapses (i.e. terminals which form more than one synapse with adjacent somata and/or dendrites). Previous studies of multiple synapse formation in the supraoptic nucleus did not include adjustments for changes in somatic size, thus the full extent of synapse formation relative to increases in cell size was not known. That multiple synapse formation is a compensatory mechanism for increased somatic size was investigated by comparing animals that were either chronically dehydrated (by drinking 2% saline) or were well hydrated. Using morphometric techniques the percentage of somatic membrane contacted by single and multiple synapses was obtained. Estimates of somatic surface area were used together with stereologically derived estimates of the number of synapses per mum(2) to calculate the number of single and multiple axo-somatic synapses per neuron. Measures of soma-somatic and soma-dendritic membrane apposition and glial coverage were made to confirm earlier estimates of these parameters. Somatic surface area increased by more than 70% in dehydrated animals. Percentage of somatic membrane contacted by single synapses was lower (by 41%) and that contacted by multiple synapses was higher (by 100%) in dehydrated as compared to control animals. The number of single synapses was not different between the two groups but dehydrated animals had more multiple synapses per soma (23) than controls (6). With dehydration, there was an eight-fold increase in the percentage of somatic membrane contacted by adjacent somatic/dendritic membrane. The surface area per somain such direct apposition was fifteen-fold higher in dehydrates compared to controls. Glial processes covered the same proportion of somatic membrane in the two groups, while the actual area covered by glial processes per soma was higher in dehydrated animals. These results are consistent with the hypothesis that multiple synapse formation at least partially compensates for probable relative decreases in synaptic efficacy as synaptic density decreases when cells increase in size due to dehydration. This altered synaptic input as well as the increased direct apposition between adjacent neurons probably contribute to their enhanced activation during periods of increased hormone demand.