T-antigen expression in 24 of 31 skin fibroblast cell lines from members of Family G was found to be significantly elevated compared with a healthy control population. However, the pattern of elevation did not appear to be associated with cancer risk. In addition, T-antigen values were independent of the age and sex, as well as the branch of family and generation of the cell donor. Cell lines from Family G tended to divide more frequently than cell lines from control donors. This tendency was negatively associated with elevated T-antigen expression in Family-G cell lines, while control cell lines showed no such correlation. These results demonstrate that caution must be taken in evaluating potential markers of cancer risk. Superficial analysis of the data would indicate the utility of the T-antigen assay as a marker for cancer family syndrome. However, consideration of additional factors, including pedigree relationships and cell biology in vitro, indicate that SV40 T-antigen expression is an ambiguous marker of this type of cancer risk, even when large groups are studied.