Meta-analyses of randomized trials evaluating cholesterol-lowering therapy have demonstrated clear reductions in coronary events and coronary mortality. However, the treatment impact on total mortality has been less certain. With the variable selection of trials and treatment questions, results of meta-analyses have sometimes given conflicting conclusions regarding the magnitude of treatment effects and the populations to whom benefits might accrue. Prospective meta-analysis can avoid these problems by clearly specifying the research questions, eligible studies, analysis plans, and outcome definitions in advance of trial results publication. This approach has been adopted in 2 major prospective meta-analyses of cholesterol-lowering treatments: the Prospective Pravastatin Pooling (PPP) project and the Cholesterol Treatment Trialists (CTT) collaboration. The PPP project is a prospectively planned combined analysis of 3 large-scale pravastatin trials comparing pravastatin against placebo over a minimum 5-year period. The analysis will contain data for > 19,500 patients and should have the power to examine the effects of treatment on total mortality, coronary mortality, and incidence of cancers as well as the ability to look at total coronary events in important subgroups underrepresented in previous trials. The CTT collaboration is a planned prospective meta-analysis of 12 major ongoing or planned randomized trials evaluating therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, a fibrate, or dietary modification. The trials were prospectively registered and the CTT protocols became final in November 1994. By the year 2000, the CTT collaboration is projected to have information on about 65,000 patients.(ABSTRACT TRUNCATED AT 250 WORDS)