Two pools of lyophilized human control serum, distributed as challenges for the 1990 and 1991 College of American Pathologists Comprehensive Chemistry Surveys were employed consecutively as two-level, daily, quality control materials in College of American Pathologists Quality Assurance Service Regional Quality Control programs. Because the Chemistry Survey and Quality Assurance Service use identical method codes and the materials are essentially stable, the variation of differences among Chemistry Survey and Regional Quality Control assay values is a sensitive measure of both the variation of accuracy among calibrator-assigned values and of the matrix response among calibrator/reagent lots following the time of initial Chemistry Survey assay. In the two cycles of data comparison, the Regional Quality Control means for the assay values of 15 stable routine chemistry analytes showed no statistically significant differences from the initial Chemistry Survey for 295 of 361 analyte-method combinations studied 16 months later. Statistically significant changes between Chemistry Survey assay values and Regional Quality Control means most often occurred with closed rather than with open analytic systems and were predominantly in the same direction at both concentration levels. The magnitude of bias difference was usually less than the average within-laboratory standard deviation for the same analyte concentration. Of 64 analyte-pool combinations studied, a single instance of probable analyte instability was noted, ie, decreasing level I glucose during the first cycle. Our findings strongly support the usefulness of Chemistry Survey-assigned target values to help strengthen the intralaboratory accuracy base. They also point out the need for and the utility of Regional Quality Control-recalculated interlaboratory means to supplement assay values assigned at the time a control pool was put into use.