Biometry Branch investigators collaborated with the Early Detection Branch and the Research Contracts Branch in implementing the major components of the PLCO Trial. This is a major trial of cancer screening in males and females for four cancers that comprise more than 50% of the incidence and mortality of cancer: lung, prostate, colorectal, and ovarian cancers. The trial design calls for a total sample size of 74,000 males and 74,000 females between the ages of 60 and 74 who are to be divided at random into a screened group and a control group. The screening techniques to be used are annual digital rectal examination and prostate specific antigen for prostate cancer, annual chest film for lung cancer, three-yearly flexible sigmoidoscopy for colorectal cancer, and annual ovarian physical examination plus CA-125 marker and transvaginal ultrasound for ovarian cancer. The Pilot Phase was completed in September 1994, during which 12,086 participants were enrolled and 4,818 screened. The Main Phase commenced in October 1994 with increased enrollment and screening. Cumulative enrollment during the current period surpassed 60,000. Data forms were modified and computers, hardware and software upgraded. Eligibility criteria were revised, quality assurance practices reassessed, and emphasis placed on minority recruitment. Procedures were developed to assess contamination in a sample of the control group and to improve medical record abstracting for followup of individuals screened positive. Initial development of approaches for using the National Death Index for mortality followup was undertaken. Preliminary data on recruitment, compliance, contamination, population characteristics, test results, and cancer cases were analyzed.