From January 1980 to July 1990, the Hospital Infections Program of the Centers for Disease Control conducted 125 on-site epidemiologic investigations of nosocomial outbreaks. Seventy-seven (62%) were caused by bacterial pathogens, 11 (9%) were caused by fungi, 10 (8%) were caused by viruses, five (4%) were caused by mycobacteria, and 22 (18%) were caused by toxins or other organisms. The majority of fungi and mycobacterial outbreaks occurred since July 1985. Fourteen (11%) outbreaks were device related, 16 (13%) were procedure related, and 28 (22%) were product related. The proportion of outbreaks involving products, procedures, or devices increased from 47% during 1980-1985 to 67% between 1986 and July 1990. Recent outbreaks have shown that packed red blood cell transfusion-associated Yersinia enterocolitica sepsis results from contamination of the blood by the asymptomatic donor; that povidone-iodine solutions can become intrinsically contaminated and cause outbreaks of infection and/or pseudoinfection; and that rapidly growing mycobacteria can cause chronic otitis media, surgical wound infection, and hemodialysis-associated infections. These and other outbreaks demonstrate how epidemiologic and laboratory investigations can be combined to identify new pathogens and sources of infection and ultimately result in disease prevention.