The safety and reliability of a system for long-term intramuscular electrical activation of the phrenic nerve was evaluated in seven dogs. In this system, electrodes are implanted bilaterally into the diaphragm without directly contacting the phrenic nerve using a laparoscope to direct placement. Five dogs underwent chronic bilateral intramuscular diaphragm stimulation (IDS) for 61 to 183 days at stimulus parameters selected to evoke at least 120% of the animal's basal ventilation. Two dogs maintained as controls did not undergo chronic stimulation. The safety and reliability of the system was evaluated in terms of tissue responses to the electrode, alterations in diaphragm muscle, pulmonary function, electrode reliability, and cardiac activation. (The efficacy of long-term intramuscular activation of the phrenic nerve is addressed in a companion paper.) No adverse responses to the electrode or stimulation were found. The histochemistry of chronically stimulated diaphragm suggested transformation towards type I (oxidative metabolism) muscle fibers. Two IDS electrodes dislodged out of a total of 32 IDS electrodes implanted. Both electrodes dislodged within seven days of implant. All IDS electrodes had stable and repeatable recruitment properties. No IDS electrode mechanical failures were found and no electrode corrosion was observed. We conclude from these experiments that intramuscular activation of the phrenic nerve will present a minimal risk to human patients who are good candidates for clinical studies using this technique.