The effects of digoxin on diaphragmatic contraction were studied in 12 sheep, within 6 days after a right thoracotomy, during the period of intense diaphragmatic inhibition. Diaphragmatic function was assessed by implanting sonomicrometry crystals and electromyographic (EMG) electrodes in both the costal and crural diaphragmatic regions. Awake sheep were studied before and after intravenous digoxin (0.04 mg/kg) during both quiet breathing (QB) and during CO2 rebreathing, until the fractional concentration of expired CO2 (FETCO2) reached 0.10. After digoxin infusion, during both QB and at FETCO2 of 0.10, esophageal and transdiaphragmatic pressures increased (P < 0.05). After digoxin infusion no changes were measured for end-expiratory resting length, shortening fraction, shortening velocity or EMG activity of either diaphragmatic segment or for respiratory frequency, ventilation, tidal volume and FETCO2. We conclude that intravenous digoxin given to awake sheep after a thoracotomy increases Pdi, but does not alter diaphragmatic shortening nor alter the level of diaphragmatic activation either during QB or at FETCO2 of 0.10.