The immunobiology of skin cancer was studied with thymus-dependent lymphocyte (T cell) levels (an in vitro measure of cellular immunity), with lymphocytic infiltration (LI) of the tumor (an in vivo measure of host-tumor relationship), and with HL-A typing (a genetic measure of histocompatibility). The T cell levels in preoperative patients with squamous (SCC) and basal (BCC) cell carcinoma were significantly lower than in the non-cancer control population (normals). The T cell levels were significantly lower in patients with large tumors than in those with small tumors. The T cell levels remained significantly low in patients cured of large tumors, but were normal in those cured of small tumors. Patients with Bowen's disease not only had T cell levels significantly lower than normal (as a group), but there was also a significant increase in the number of patients who had T cell levels less than two standard deviations below the normal mean. This may signify that they have a greater risk of developing a second kind of malignancy elsewhere. There was a direct correlation between the degree of lymphocytic infiltration (LI) of the tumor, the tumor size, and the T cell level. Small, well-localized tumors had a marked LI and high T cell levels--while the large, deeply invasive tumors had a minimal, or absent, LI and low T cell levels. The presence of HL-A antigens 1 and 8 correlated both with a tendency toward large tumors and with low T cell levels. This may represent the association of a human immune response gene with the human histocompatibility locus. Possibilities for the application of these findings in the clinical management of skin cancer are discussed.