From a random sample of patients and hospitals and extrapolation ratios derived from the best available sources of data, the authors estimate that the nationwide nosocomial infection rate among the 6,449 acute-care US hospitals in 1975-1976 was 5.7 nosocomial infections per 100 admissions and that over 2 million nosocomial infections occurred in a 12-month period in these hospitals. Nosocomial urinary tract infections constituted 42% of the infections, surgical wound infections 24%, nosocomial pneumonia 10%, nosocomial bacteremia 5%, and nosocomial infections at all other sites 19%. If adjustments are made for the accuracy of the diagnostic method, the increasing nationwide secular trend, and the number of nosocomial infections in nursing homes, however, as many as 4 million nosocomial infections per year may now be occurring. This greatly exceeds previous estimates and calls for timely and accurate vital statistics on the problem.