Pseudomonas aeruginosa strains isolated from cystic fibrosis patients were tested for production of exoenzymes, sensitivity to pooled normal human serum, and colony morphology. Strains isolated from patients exhibiting a severe form of the disease were seen to produce a decreased range of exoenzymes, to show an increase in their serum sensitivity, and to be predominantly mucoid in colonial character compared with strains isolated from patients with a milder form of the disease. These results suggest that P. aeruginosa undergoes phenotypic changes with respect to exoenzyme secretion, serum sensitivity, and colony form as the clinical condition of the cystic fibrosis patient changes.