The aims of this study are twofold. The first is to describe the ultrastructural morphology of putative osmoreceptors concentrated in the ventral aspect of the lamina terminalis in the rat forebrain. The second is to determine whether or not these neurons lie within an area which lacks a blood-brain barrier, i.e. the organum vasculosum lamina terminalis. The results describe a compact population of neurons in the ventral part of the lamina terminalis which both respond to an osmotic challenge and project directly to the supraoptic nucleus. Injection of horseradish peroxidase into the circulation, as a marker to define areas of the brain without a blood-brain barrier, indicates that these neurons are in the dorsal aspect of the organum vasculosum of the lamina terminalis. An ultrastructural analysis of the neurons in this area, which respond to an osmotic challenge with an elevation of Fos protein, show them to have no specific morphological characteristics which differentiate them from other, non-responsive neurons in the organum vasculosum of the lamina terminalis. However, one possible exception is that osmotically sensitive neurons have a less indented nucleus, suggesting that they are in a more active state than their non-osmotically sensitive neighbours. It is concluded that neurons in this region of the brain are candidate structures for the ''receptors'' which mediate vasopressin release in response to an osmotic challenge. The response of only a subset of neurons in the organum vasculosum of the lamina terminalis to an osmotic stimulus, despite an apparent morphological homogeneity and the ability of blood borne agents to reach all parts of the structure suggests that osmoresponsiveness is conferred by unique membrane properties or intracellular processing events. The presence of synaptic input to osmoresponsive cells indicates a potential for integration of other inputs at this level.