Since the majority of germline mutations in the TP53 gene seem to occur in LFS or LFL families, and these are rare, research is best conducted in a collaborative setting (Li and Fraumeni, in press). In a report from a meeting at Bethesda in 1993, the following areas were outlined for collaborative study: the correlation (if any) of phenotypes with specific mutation; age specific penetrance; cumulative cancer incidence; gender differences in tumour development in carriers; the effects of DNA damaging agents on individuals with a TP53 mutation; the frequency of TP53 germline mutations in cohorts of patients with rare childhood tumours (eg adrenocortical carcinoma); and the psychosocial aspects of predictive TP53 testing. In addition, if, as seems likely from recent data, X irradiation in these individuals induces DNA damage that is tolerated, urgent collaborative studies are needed to investigate new methods of screening, such as magnetic resonance imaging. Treatment modalities should be carefully chosen, and for this reason alone, predictive testing may be desirable in all LFS and LFL families. Individuals carrying TP53 mutations could be offered chemoprevention within trials in an effort to reduce their mortality from cancer.