A long term (20 day) pediatric ventilator model was developed using 3 month old beagles. Canis familiares beagle was selected because it (1) is a standard toxicology model, (2) has been used as a pediatric model, (3) is about 5-6 kgs, biologically safe, easy to care for and instrument and, (4) some experience in long term (3 day) conventional ventilator (CV) management was available. The study required continuous sedation, ventilation (Siemens Servo 300) and nutrition for 6 to 10 days, infection control and weaning to normal activity. A pilot run of 5 animals was performed and validated on an additional 13 animals. Study groups included: (1) CV 6 days, never weaned, (2) CV 10 days, never weaned and (3) CV 6 days, weaned, and necropsied at day 20. Infection was the most common problem in all groups. 3 of 5 pilot animals died at day 3, 5 and 8 of E. Coli, Strept species and Klebsiella. Attention to good oral care with chlorhexidine mouth wash every 12 hours, Timentin from day -1 to 5 with the addition of Gentamicin for signs of infection in the first 5 days, automatic change to Vancomycin, Amikacin and Cefotaxime at day 6, and q2hr rotation of the animals prevented infection related deaths in the main 13 animals. Sedation failed using fentanyl, other narcotics and Ketamine. Paralysis created problems with fluid management and clinical evaluation. A pentobarbital infusion achieved adequate sedation, but resulted in seizures upon weaning (1 confirmed, 2 probable), withdrawal ataxia (all animals) and GI ileus (all animals). Seizures were easily controlled with phenobarbital, TPN provided nutrition with GI motility returning within 24 hours of pentobarbital discontinuation. All animals required increasing pentobarbital doses which plateaued after the first 5 days. A defective lot of pentobarbital caused clotting problems in several main study animals. All group 3 animals weaned from the ventilator and were taking solid food within 48 hr. All animals walked by 2-4 days, and at 20 days had returned to normal activity. Groups 1 and 2 remained sedated and ventilated without significant problems.Funded: Alliance Pharm Corp & Hoechst Marion Roussel