Structural enhancement of nerve cell morphology has been postulated to be an integral step in the cellular process leading to information storage in the nervous system. To investigate this postulate, we determined whether vasopressin (AVP), a neural peptide that can enhance memory function, would enhance the cytoarchitectural features of hippocampal neurons in culture. Results of these studies demonstrated that in the presence of serum, vasopressin (1 microM), induced a significant increase in the number of neurites, in neuritic length, and in neurite diameter following 48 h of exposure. Morphological complexity was also enhanced following vasopressin exposure as indicated by a significant increase in the number of filopodia/branches, in the sum of branch lengths, and in the number of branch bifurcation points. The number of microspikes decorating neuritic branches was also significantly increased following vasopressin exposure. To determine whether the neurotrophic effect of vasopressin was dependent upon factors present in serum, hippocampal nerve cells were cultured in serum-free media and exposed to 100-1000 nM AVP. Results of these studies demonstrated that in the absence of serum, AVP induced significant enhancement of hippocampal nerve cell growth and that the minimally effective concentration was reduced from 1 microM, as required in the presence serum, to 100 nM. In addition, the time required for a significant increase in nerve cell growth to become apparent decreased from 48 to 24 h. These results demonstrate that AVP-induced neurotrophism is not dependent upon unidentified factors in serum. AVP-induced neurotrophism was found to be mediated by V1 receptor activation. Significant enhancement of nerve cell growth occurred following exposure to V1 receptor agonist (100-1000 nM), whereas exposure to V2 receptor agonist (100-1000 nM) did not increase any of the morphological parameters measured. Considered together, these data indicate that vasopressin can exert a significant neurotrophic effect upon hippocampal nerve cells in culture. Moreover, AVP-induced neurotrophism is a direct effect and not dependent upon unidentified factors present in serum. Enhancement of hippocampal nerve cell growth occurred in the presence of a specific V1 receptor agonist and not following exposure to a V2 agonist, suggesting that activation of the phosphatidyl inositol pathway via V1 receptor activation mediates AVP-induced neurotrophism. Results of these studies are discussed with respect to their implications for understanding vasopressin involvement during neural development and induction of cytoarchitectural modifications associated with memory formation.