The effects of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep were compared in six patients with chronic obstructive lung disease and carbon dioxide retention. Patients received 1.5 mg/kg almitrine (a peripheral chemoreceptor stimulant), 100 mg of medroxyprogesterone (a central respiratory stimulant), or matched placebo daily for 15 days in random order in a crossover trial. When subjects were awake almitrine increased the ventilatory response to hypoxia and increased arterial oxygen tension (PaO2) to a greater extent than medroxyprogesterone, whereas medroxyprogesterone augmented the ventilatory response to hypercapnia and decreased arterial carbon dioxide tension (PaCO2) to a greater extent than almitrine. Neither drug influenced sleep architecture significantly, except that medroxyprogesterone increased the number of arousals. Almitrine had a more favourable effect than placebo on oxygenation as estimated from arterial oxygen saturation (SaO2) during the different stages of sleep, the number of episodes of hypoxaemia, and the amount of time that SaO2 was below 80%. The only change with medroxyprogesterone by comparison with placebo was a decrease in the number of hypoxaemic episodes. It is concluded that both active drugs improved blood gases during wakefulness, but that 1.5 mg/kg of almitrine is superior to 100 mg of medroxyprogesterone in improving SaO2 during sleep.