The effect of enteral nutrition with different protein contents on metabolic and ventilatory variables during weaning from the ventilator was studied in 10 mechanically ventilated patients as indication of the effect of protein on the ventilatory drive. Resting energy expenditure (R.E.E.) was assessed in the post-absorptive state and 2 enteral regimens both with a fat and carbohydrate content 1.25 times R.E.E. but with a moderate (190 mg N/kg/24 h) and high (260 mgN/kg/24 h) protein content were given to the patients in random order. Minute ventilation (V̇ E), CO 2-production (V̇CO 2), O 2-consumption (V̇O 2) and arterial blood-gases were obtained during mechanical ventilation and weaning. Compared with post-absorptive state, both intakes gave significant increases in V̇CO 2 during mechanical ventilation; the V̇CO 2 values were equal for both regimens before the start of the weaning procedures. High protein intake was associated with significantly higher V̇CO 2 during weaning and smaller increases in p aCO 2 from mechanical ventilation to the end of the weaning-period, compared with the moderate protein intake. This result is in agreement with studies in which an infusion of amino-acids in spontaneous breathing healthy volunteers increased ventilatory sensitivity to CO 2. For mechanically ventilated patients high protein nutrition may be beneficial in enhancing weaning from the ventilator.