Background: Methicillin-resistant Staphylococcus aureus has become a frequent cause of hospital-acquired infectious disease. However, the impact of methicillin-resistant S. aureus on the overall nosocomial infection rate has not been clearly defined. Methods: The University of Alabama at Birmingham Hospital is a tertiary care facility and participant in the National Nosocomial Infections Surveillance system. Prospective, hospital-wide surveillance for nosocomial infections was conducted for 8 months per year during 1986 through 1991. Results: The total nosocomial infection rate increased from 4.5% in 1987 to 5.9% in 1990. This was temporally associated with a rise in the attack rate of methicillin-resistant S. aureus from 0% to 0.4%. The remainder of the increase was caused by other gram-positive microorganisms, including methicillin-sensitive S. aureus. We identified methicillin-resistant S. aureus most commonly in the surgical intensive care unit and as a cause of lower respiratory tract infections. In contrast, methicillin-sensitive S. aureus was most frequently found in the neurologic intensive care unit and as the etiologic agent of surgical wound infections. Conclusions: Methicillin-resistant S. aureus has become a common nosocomial pathogen. There has been no decrease in the attack rate of methicillin-sensitive S. aureus or other gram-positive cocci. The total nosocomial infection rate has increased as a result equally of the emergence of methicillin-resistant S. aureus and of the renewed activity of other gram-positive pathogens. Methicillin-resistant S. aureus has added to the overall burden of nosocomial infectious disease. © 1993.