Fifty nevomelanocytic lesions, including 10 typical compound nevi and 20 radial and 20 vertical growth-phase melanomas, were evaluated for factor XIIIa and HLA-DR (LN3) expression within dermal dendritic cells (DDCs) or dermal dendrocytes to determine if DDCs proliferate and/or participate as possible antigen-presenting cells in the local tissue response to benign and malignant nevomelanocytic lesions. There was no statistical difference in factor XIIIa staining of DDCs between nevi and radial or vertical growth-phase melanomas, suggesting that DDCs do not significantly proliferate in nevomelanocytic lesions. However, studies to determine proliferation rate, apoptosis, and influences of local mediators on cell growth and/or recruitment were not done. HLA-DR staining by DDCs was significantly increased (p<0.001) in both melanoma groups when compared to compound nevi, but did not significantly differ between radial and vertical growth-phase melanomas. The intensity of HLA-DR expression appeared to correlate with the presence or absence of lymphocytic inflammation; HLA-DR intensity was judged greater in melanomas characterized by a brisk and infiltrative lymphocytic host response. We propose that DDCs may participate in the dermal immune response to invasive melanomas, probably as antigen-presenting cells to skin-associated lymphocytes.