Volunteers for prevention or screening trials are generally healthier and have lower mortality than the general population. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) is an ongoing, multicenter, randomized trial that randomized 155,000 men and women aged 55-74 years to a screening or control arm between 1993 and 2001. The authors compared demographics, mortality rates, and cancer incidence and survival rates of PLCO subjects during the early phase of the trial with those of the US population. Incidence and mortality from PLCO cancers (prostate, lung, colorectal, and ovarian) were excluded because they are the subject of the ongoing trial. Standardized mortality ratios for all-cause mortality were 46 for men, 38 for women, and 43 overall (100 = standard). Cause-specific standardized mortality ratios were 56 for cancer, 37 for cardiovascular disease, and 34 for both respiratory and digestive diseases. Standardized mortality ratios for all-cause mortality increased with time on study from 31 at year 1 to 48 at year 7. Adjusting the PLCO population to a standardized demographic distribution would increase the standardized mortality ratio only modestly to 54 for women and 55 for men. Standardized incidence ratios for all cancer were 84 in women and 73 in men, with a large range of standardized incidence ratios observed for specific cancers.