Perfluoro-n-butyl iodide (PFBI) is a promising alternative to chlorofluorocarbon solvents used in aircraft ground maintenance operations and other military and commercial operations, because it cleans well, has zero ozone depletion potential, and has extremely low global warming properties. Toxicity tests were performed with PFBI to determine and evaluate its health hazard. Using standard testing guidelines (e.g., Organization for Economic Cooperation and Development [OECD]), tests included acute (4-h) and 4-week (6 h/day, 5 days/week) inhalation (nose-only) toxicity studies in rats, acute (10-min) inhalation cardiac sensitization study in dogs, in vitro chromosomal aberrations experiments in human lymphocytes, and in vitro mutagenic experiments in Salmonella typhimurium and Escherichia coli. There were no mortalities in rats (n = 10) exposed for 4 h to 10,000 ppm PFBI, but all rats (n = 10) died within 2 h when exposed to 20,000 ppm PFBI. The 4-h LC50 (95% confidence limits) was 14,000 ppm (13,000 ppm to 16,000 ppm). Signs (nasal discharge and labored breathing) observed in the rats exposed to 10,000 ppm returned to normal within 48 h. PFBI has the potential to cause cardiac sensitization in epinephrine-challenged dogs at 6200 ppm. A concentration of 3900 ppm was a no-observed-adverse-effect level (NOAEL) in the cardiac sensitization study. In the 4-week inhalation study (5 rats/sex/group), respiratory mucosal hypertrophy/hyperplasia was observed in rats of the 10,000-ppm group. A NOAEL of 1000 ppm was selected for the 4-week study on the basis that the mild increase in T4 observed at 1000 ppm was considered adaptive, not adverse, because of the absence of frank effects in the thyroid. In the in vitro studies, PFBI showed no evidence of either mutagenic or clastogenic activity. The toxicity profile of PFBI was compared to trifluoroiodomethane. In conclusion, the results of these studies indicate a low order of general toxicity and an absence of genotoxicity following PFBI exposure.