Microbial biotechnology applications have prompted research into their potential impacts on human health and the environment. In this study, a mouse model was used to evaluate indirect effects (e.g., alteration of the intestinal microbiota) of pulmonary exposure to representative biotechnology agents (Pseudomonas aeruginosa strain AC869 and Pseudomonas cepacia strain AC1100) selected for their ability to degrade hazardous chemicals. CD-1 mice were challenged intranasally with approximately 1,000 or 10 to the 7th power colony-forming units (cfu) of strain AC869 or 10 to the 8th power cfu of strain AC1100. At time intervals, clearance of the microorganisms and effects on resident microbiota were determined. When the low (1,000 cfu) dose was administered, strain AC869 was not recovered from the small intestine but was detectable in the cecum and lungs 3 h after treatment and persisted in the nasal cavity intermittently for 14 d. Treatment of animals with 10 to the 7th power cfu of strain AC869 resulted in detection 14 d following treatment. Strain AC869 challenge modified the small intestinal anaerobe count and cecal obligately anaerobic gram-negative rods (OAGNR) and lactobacilli. Following exposure, Pseudomonas cepacia strain AC1100 persisted in the lungs for 7 d and was recovered from the small intestine, cecum, and nasal cavity 2 d following treatment. Strain AC1100 treatment impacted the small intestinal anaerobe count, OAGNR counts, and reduced lactobacilli numbers. Strain AC1100 also altered the cecal OAGNR and lactobacilli.