Nocturnal desaturations during rapid eye movement (REM) sleep, caused by nonobstructive hypoventilation, occur frequently in patients with chronic obstructive pulmonary disease (COPD). This is partly caused by decreased activity of the intercostal and accessory muscles due to a lower motor command. The diaphragm has to compensate for the diminished activity of these muscles during REM sleep. However, in patients with COPD strength and endurance of the diaphragm may be affected by its unfavorable position on the length-tension curve because of hyperinflation. The aim of this study was to establish the causal relationship between respiratory muscle function and nocturnal saturation in patients with COPD. We hypothesized that target-flow inspiratory muscle training (TF-IMT) would improve nocturnal saturation. In 20 patients with stable COPD (FEV1 35.5 +/- 14.1% of predicted) and a mean nocturnal saturation below 92% we measured maximal inspiratory pressure (PImax), transdiaphragmatic pressure (Pdi), maximal sustainable inspiratory pressure (SIPmax), endurance time, and nocturnal saturation in Weeks 0, 4, and 10. During these 10 wk 10 patients underwent TF-IMT at 60% of PImax and 10 control patients received sham TF-IMT at 10% of PImax. PImax, Pdi, SIPmax, and the endurance time as well as the nocturnal saturation improved significantly in the 60% training group (by 3.0 +/- 1.5 kPa, 3.4 +/- 1.9 kPa, 1.5 +/- 1.4 kPa, 189 +/- 149 s, and 1.9 +/- 2.2%, respectively), whereas no changes occurred in the sham training group. Also, significant correlations were observed between the changes in Pdi, SIPmax, and endurance time on the one hand and the change in nocturnal saturation on the other. We conclude that TF-IMT improves the nocturnal saturation in patients with severe COPD by increasing respiratory muscle strength and endurance.