We tested the effectiveness of specific vs. general infection control interventions in a teaching hospital in Guatemala City. After 3 months of prospective surveillance, we implemented targeted interventions (i.e., modification of respiratory tract care and use of a closed urinary catheter drainage system), an educational program focused on respiratory intervention, and general interventions (i.e., aseptic technique). The rate of nosocomial pneumonia, the most common nosocomial infection, decreased from 33% (41 of 123 patients) before intervention to 16% (21 of 130 patients) after intervention (P = .001). Although the frequency of hand washing increased from 5% to 63% (P < .001), the rates of other types of nosocomial infections did not change significantly. The combination of targeted respiratory intervention and an intense, focused educational campaign reduced the rate of nosocomial pneumonia. General improvements in hygiene and hand washing rates, or even implementation of a closed urinary drainage system without focused education, may not be sufficient to reduce infection rates in intensive care units in developing countries.