The binding of histamine to cultured microvascular endothelial cells and glycol methacrylate embedded ovarian tissue sections has been localized using fluorescein-albumin-histamine conjugate. Histamine conjugate was bound to the plasma membranes and nuclei of luteal, endothelial, and ovarian stromal cells. An apparent increase in the binding of histamine to nuclei was observed in the presence of cimetidine but the plasma membrane staining was still evident. Unlike cimetidine, pyrilamine completely inhibited the binding of histamine to the plasma membrane. Instead, in the presence of pyrilamine, histamine bound exclusively to the nuclei of endothelial, germinal epithelial, granulosa, and stromal cells. However, the nuclei of terminally differentiated luteal cells and oocytes were not labeled. The functional significance of these nuclear histamine binding sites remains to be determined.