OBJECTIVE To determine whether nosocomial transmission of Pseudomonas cepacia occurred at a hospital with endemic P cepacia infection of patients with cystic fibrosis. METHODS Two retrospective case-control studies. METHODS A large pediatric cystic fibrosis center. METHODS To assess risk factors for acquisition of P cepacia, 18 cases, defined as any patient with cystic fibrosis with first documented isolation of P cepacia in 1988 or 1989, were compared with 18 matched P cepacia-negative controls with cystic fibrosis. To assess potential modes of nosocomial P cepacia transmission, 14 cases with a hospitalization(s) between their last P cepacia-negative culture and first P cepacia-positive culture were compared with 14 hospitalized P cepacia-negative controls with cystic fibrosis. METHODS Handwiping cultures (N = 68) and selective environmental cultures were performed. RESULTS Cases tended to be more likely than controls to have been hospitalized at the cystic fibrosis center in the 3 months before their first P cepacia-positive culture (P = .08). In addition, cases tended to be more likely than hospitalized controls with cystic fibrosis to have had a P cepacia-positive roommate (P = .06) before becoming colonized with P cepacia organisms. Pseudomonas cepacia was cultured from the hands of two individuals: a P cepacia-colonized patient who had just undergone chest physiotherapy and consequent coughing and the investigator who shook the P cepacia-positive patient's hand after the patient's procedure. CONCLUSIONS These results suggest that in this cystic fibrosis center, hospitalization is a risk factor for P cepacia acquisition and that person-to-person transmission of P cepacia may occur in the hospital via hand contact.