The immunophenotype of tumor cells and inflammatory infiltrate associated with cutaneous melanocytic lesions (29 melanocytomas, two malignant melanomas, and 23 residual lesions) from 54 adult Iberian and Iberian x Duroc pigs were examined using a panel of nine antibodies. All neoplastic cells were vimentin+, cytokeratin-, and alpha-1-antitrypsin- and the majority were S100+, whereas all pigmented macrophages were vimentin+, cytokeratin-, and S100- and most expressed alpha-1-antitrypsin. Regressing tumors were characterized by zones with low density of neoplastic cells accompanied by heavy infiltration of CD3+ T lymphocytes, whereas zones with high density of neoplastic cells showed very low numbers of CD3+ T lymphocytes. The infiltrate of CD79a+ B cells and IgG, IgM, and IgA plasma cells was low. The majority of lymphocytes of the peri- and intratumoral infiltrate were major histocompatibility complex class II+, but neoplastic cells did not express class II antigen. The 17 residual lesions examined were composed of macrophages containing abundant melanin pigment and low to moderate numbers of CD3+ T lymphocytes. The results of the present study suggest that the local cellular immune response plays a crucial role in the host response that induces regression of cutaneous melanomas and melanocytomas of the Iberian and crossbred Iberian x Duroc pigs.