In 1994 we investigated a large outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract acquisition. A case patient was defined as any patient with at least one sputum culture from which B. cepacia was isolated from 1 January to 31 December 1994. Seventy cases were identified. Most (40 [61%]) occurred between 1 February and 31 March 1994; of these, 35 (86%) were mechanically ventilated patients, 30 of whom were in an intensive-care unit (ICU) when B. cepacia was first isolated. Compared with control patients who were mechanically ventilated in an ICU, these 30 case-patients were significantly more likely to have been ventilated for 2 or more days (30/30 v. 15/30; P < 0.001) or to have been intubated more than once (12/30 v. 2/30; OR = 9.3, 95% CI 1.6-68.8; P = 0.002) before the first isolation of B. cepacia. By multivariate analysis, the 35 mechanically ventilated case-patients were significantly more likely to have received a nebulized medication (OR = 11.9, 95% CI = 1.6-553.1; P < 0.001) and a cephalosporin antimicrobial (OR = 11.9, 95% CI = 1.6-553.1) in the 10 days before the first isolation of B. cepacia, compared with B. cepacia-negative control-patients matched by date and duration of most recent mechanical ventilation. Although B. cepacia was not cultured from medications or the hospital environment, all outbreak strains tested had an identical DNA restriction endonuclease digestion pattern by pulsed-field gel electrophoresis. Review of respiratory therapy procedures revealed opportunities for contamination of nebulizer reservoirs. This investigation suggests that careful adherence to standard procedures for administration of nebulized medications is essential to prevent nosocomial respiratory infections.