The altered function of respiratory muscle function in chronic obstructive pulmonary disease (COPD) has been documented by short term studies but not by prospective follow-up. To evaluate the progression of muscle dysfunction and its relation to hyperinflation, air flow obstruction and generalized muscle weakness, we studied seven patients upon admission and 10 to 25 months later. We measured peak inspiratory (PImax) and expiratory (PEmax) pressures in the mouth, peak pleural inspiratory pressure (Pplimax) and peak transdiaphragmatic pressure (Pdimax). Pdimax was measured using gastric (Pg) and esophageal (Ppl) balloons. The slope of excursion of Pg and Ppl measured at the end of inspiration and expiration (Pg/Ppl) was used to assess respiratory muscle recruitment. Nutritional status was indexed as the ratio of weight to height (W/H). FEV1 remained unchanged (1.0 +/- 0.1 to 0.8 +/- 0.3 L), while functional residual capacity (FRC) increased from 7.1 +/- 1.0 to 8.9 +/- 2.0 L (p < 0.05). W/H, PImax, Pplimax and PEmax remained unchanged, while Pdimax decreased significantly from 83 +/- 35 to 47 +/- 16 cmH2O. Diaphragm loading (TTDI and Pdi/Pdimax) were found to increase and Pg/Ppl shifted toward increased use of accessory muscles. The last finding was significantly related to changes in FRC (r = 0.87; p < 0.05). We conclude that diaphragm function deteriorates progressively in patients with severe COPD, even though overall inspiratory muscle strength is preserved, apparently as a consequence of the effect of mechanical factors (hyperinflation) but not of air flow obstruction or generalized muscle weakness.