The main objective of the Study on the Efficacy of Nosocomial Infection Control (SENIC Project) is to determine whether infection surveillance and control programs have reduced the rates of nosocomial infection in United States hospitals. To study this question, we stratified all hospitals in the SENIC target population into 16 design strata defined by categories of a surveillance and a control index derived from hospitals' responses to a preliminary screening questionnaire, and estimated the nosocomial infection rates among 339,044 randomly selected patients admitted in 1970 and 1975 through 1976 to 338 hospitals selected randomly from the 16 design strata. Finding that the over-all infection rates, standardized for important confounding variables or covariates, in hospitals with higher intensity programs had increased less from 1970 to 1975-1976 than those of hospitals with low intensity programs would indicate the efficacy of these programs. Potentially important confounding variables and covariates being studied include individual patient risk factors, hospital characteristics and the completeness of hospitals' medical records. Since only the first has been explored sufficiently, no conclusions on efficacy can yet be drawn. The analytic techniques were illustrated with preliminary data on infection rates at the four individual sites of infection.