We measured in rats the effects of 48 h of mechanical ventilation on the weight, contractile properties, and enzymatic profile of the diaphragm, the soleus and the extensor digitorium longus (EDL) muscles. Eighteen animals were randomly divided into a mechanically ventilated (MV, n = 9) group or a control (C, n = 9) group. During the 48 h of mechanical ventilation, animals in the MV group were anesthetized with sodium thiopental and enterally fed with a gastric catheter. Group C animals were neither anesthetized nor mechanically ventilated during the 48-h experimental period, and they had access to food and water ad libitum. Muscular contractile properties were measured in vitro by analysis of force-frequency curves and twitch characteristics. The weights of the three muscles were significantly reduced in the MV group compared with those in the C group. This was accompanied in the diaphragm by a reduction in the normalized force generated for all the frequencies of stimulation, except 20 Hz, whereas twitch characteristics were not modified. The forces generated by the soleus and EDL were not significantly reduced in the MV group compared with those in the C group. Diaphragm, soleus, and EDL citrate synthase and lactate dehydrogenase activities were not significantly different in the two groups. We conclude that mechanical ventilation for 48 h in rats produces a selective force reduction in the diaphragm.