This is a proposal for continuing support of a large prospective study begun in 1975 to determine 1) the incidence and relative risk of primary hepatocellular carcinoma (PHC) among hepatitis B virus (HBV) carriers, and 2) the feasibility of annual alpha fetoprotein AFP screening for the detection of early small removable tumors. The basic population is 22,707 Chinese government employees in Taiwan among whome 15% are HBsAg carriers and PHC and/or cirrhosis accounts for 20% of all deaths. We have virtually total assertainment of death because government employees all have life insurance. Cause of death can be accurately determined because they all have total coverage medical insurance and almost always obtain care at the best medical centers where excellent diagnostic workups are routinely undertaken. Seventy of 71 PHC cases occurring to date have been among HBsAg carriers (relative risk 390). Continuation of this study will permit evaluation of other factors which may contribute to risk. We obtain 95% adherence to annual followup for AFP testing and have a cohort of 5200 HBsAg carriers in our screening program. Serum AFP values regularly become elevated when tumors are tiny and continue to rise as tumors grow. In our hands this test has: sensitivity = 80.6%, Specificity = 99.97%, Predictive power of postive test = 89.3%, Predictive power of negative test = 99.94%. Thirty of 32 surgical resections to date have been successful, but followup has been too short to evaluate long term benefit. Three patients are living and well more than two years following resection, however. The main purpose of this project is to determine the long term success of AFP screening and to refine the criteria for its use.