The purpose of this pilot study was to determine if N-acetylcysteine (NAC) administered via the rectal route in swine is absorbed into the systemic circulation. Fasting swine were anesthetized, intubated, monitored and i.v. access was obtained by femoral cutdown. NAC was administered into the rectal vault (2.0 g/kg) via a balloon-tipped Foley catheter inserted into the animals' rectum. NAC administered via the rectal route resulted in systemic absorption as determined by spectrophotometric methods in 5 of the 7 study animals. This study provides important information regarding the development of a potential alternative route for the administration of NAC.