Pseudomonas cepacia colonization among patients with cystic fibrosis (CF) at our center has increased from 7% (of 419 patients) to 15% (of 450 patients) over the past 5 yr (July 1978 through June 1983). The proportion of patients dying with P. cepacia colonization has increased over this 5-yr period (Year 1, 9% (1/11) of the deaths were associated with P. cepacia; Year 5, 55% (16/29) were associated with P. cepacia). These observations have led to a heightened concern regarding the presence of P. cepacia in the CF population. Characteristics of the patient population that might relate to P. cepacia colonization were reviewed. Increasing numbers of patients in good clinical condition became colonized with P. cepacia. Females in good clinical condition who acquire P. cepacia appear to be at special risk of developing severe and unexpected pulmonary complications that often end in death. In contrast, males, regardless of clinical condition, appear less likely to experience an immediate decline in clinical status. Hospitalization is potentially implicated in contributing to the increase in P. cepacia colonization because many patients' initial positive cultures were concurrent with or followed a hospital stay. Sixteen patients with CF and P. cepacia had siblings with CF, 6 of whom subsequently acquired P. cepacia. This frequency is more than double that in our overall CF population.