To assess the effects of long-term nasal continuous positive airway pressure (CPAP) in occlusive sleep apnea syndrome (OSA), 17 patients with severe symptomatic OSA had repeated spirometry, arterial blood gases, and nocturnal polysomnograms off nasal CPAP after 3 to 46 months of treatment with nasal CPAP. Without loss of weight or change in respiratory mechanics, the ventilatory disturbance index fell from a mean of 87 events per hour to 57 events per hour (p<0.0001), correlating with an improvement in mean nocturnal desaturation with sleep-disordered breathing events (r=0.54, p=0.03). Moreover, the daytime PaO2rose significantly from a mean of 69 mm Hg to a mean of 82 mm Hg (P=0.0001) at follow-up. The rise in daytime PaO2was not only due to the alleviation of daytime hypercapnea observed in eight of nine hypercapneic subjects since the P(A-a)O2gradient also decreased significantly. The improvement in PaO, correlated significantly with the number of months of CPAP therapy, suggesting a continuing effect over time (r=0.58, p=0.015). These results indicate that there is a reversible element of the severity of OSA and suggest a result of nasal CPAP therapy may be to reverse the adverse and time-dependent effects of hypoxemia and sleep fragmentation on ventilatory control in severe OSA.