Four days after corneal inoculation of mice with herpes simplex (type 1) virus (HSV), infected trigeminal ganglion cells with and without calcitonin gene-related peptide (CGRP) antigenicity were examined by electron microscopy in sections treated with colloidal gold labeled antibodies. Cells that contain CGRP were identified by the dense gold labeling of small vesicles about 100 nm in diameter. Adjacent thin sections were stained using an indirect colloidal gold immunocytochemical technique to reveal HSV-1 antigens. In CGRP-positive neurons, HSV antigens were located over both nuclear and cytoplasmic compartments. HSV label was found over cytoplasmic vesicles that were significantly larger than those labeled with anti-CGRP antisera; the HSV-containing vesicles ranged in profile diameter from less than 170 to greater than 400 nm. There was no overlap in the distribution of the two labels. Thus, for this time period, the organelles involved in transport of the endogenous neuropeptide and HSV appear to remain discrete. Furthermore, there was no significant difference in the distribution of HSV in CGRP-reactive and CGRP-negative trigeminal ganglion cells. Thus, there is no indication of a preferential distribution or limited replication of HSV in CGRP-positive neurons.