Fifty basal cell carcinomas (BCC) and 8 samples of healthy skin were studied for HLA class I and class II antigen expression and for the presence of mutations in codon 12 of the K-ras and H-ras genes. All samples of healthy skin and of epithelium near the tumor showed high levels of class I molecules, whereas 38% of the tumors showed complete absence. Sixty-two percent of the tumors presented positive class I expression with heterogeneous staining. These losses were due to the simultaneous lack of heavy chain and beta 2-microglobulin. Selective losses of HLA-A or HLA-B antigens were not detected. Class II antigens were absent in most of the tumors, only two tumors showing a few weakly positive cells with anti-HLA-DR mAb. The loss of class I expression correlated significantly with the degree of histological differentiation and aggressiveness. We were unable to correlate class I expression with clinical size, depth of invasion or the extent of leukocytic infiltrate surrounding the tumor. Analysis by PCR amplification of codon 12 of the K-ras and H-ras oncogenes detected H-ras mutations in 1 out of 50 cases, and no K-ras mutations in any of the tumors studied. Thus, a positive relationship between K-ras and H-ras mutations and BCC tumorigenesis or MHC alterations seems unlikely in this neoplasia.