The effects of corticosteroid administration for 2 weeks on diaphragm histology, biochemistry, and function were assessed in the rabbit at rest and during inspiratory loading to respiratory failure, and compared to the extensor digitorum longus and untreated control animals. There were marked pathologic changes in the diaphragm after corticosteroid administration and significant alterations in diaphragm glycogen level (118.7 +/- 2.8 versus 56.2 +/- 1.0 mmol/kg wet weight, p less than 0.01) and lactate level (5.3 +/- 0.3 versus 3.5 +/- 0.4 mmol/kg wet weight, p less than 0.01) with only minimal changes in the skeletal muscle. Although respiratory muscle endurance in the control group increased from 142 +/- 17 min at baseline to 155 +/- 20 at Week 1 and 183 +/- 13 at Week 2 (p less than 0.05), it fell progressively from 135 +/- 19 min at baseline to 99 +/- 5 at Week 1 and 88 +/- 9 at Week 2 (p less than 0.01) in the corticosteroid-treated animals. On the other hand, there was no significant change in resting Pdimax after corticosteroid administration. In addition, there was no significant change in Pdimax, Pdi/Edi ratio, or glycogen level at the point of respiratory failure, but diaphragm lactate levels were increased (8.5 +/- 0.8 versus 5.3 +/- 0.3, p less than 0.05). When variable degrees of diaphragm dysfunction were induced by phrenic nerve pacing and/or thoracoabdominal binding, the degree of biochemical change associated with diaphragm dysfunction was significantly greater in corticosteroid-treated animals. We conclude that corticosteroid administration in the rabbit alters diaphragm histopathology and biochemistry as well as respiratory muscle endurance, but not strength.(ABSTRACT TRUNCATED AT 250 WORDS)