1. Cardio-pulmonary responses and gas exchange during progressive exercise, the ventilatory response to hypercapnia and anthropometric indices were measured in twenty-two Jamaican adults with homozygous sickle-cell disease. Their anthropometric indices and exercise performances were compared with those observed in healthy but sedentary adults in the Caribbean.2. The patients had long lower limbs for their height; their body fat, proportion of lean body mass as muscle and vital capacity were reduced. Haemoglobin concentrations ranged from 4 to 10 g/lOO ml. Heart rate and ventilation were normal at rest.3. During exercise in the male patients haemoglobin concentrations below about 8 g/100 ml were associated with an increased demand for anaerobic metabolism. This resulted in excessive lacticacidaemia and increased ventilation at standard oxygen uptake (hyperpnoea). The ventilation-tidal volume relationship was normal. When allowance was made for differences in body muscle, anaemia did not appear to affect the heart-rate response to exercise. 4. Hyperventilation with respect to carbon dioxide output, increased alveolararterial oxygen-tension gradients and abnormal deadspace ventilation during exercise indicated a pulmonary perfusion disturbance with mixed venous shunting. The most likely basis for this disorder was considered to be the sickling phenomenon. Arterial hypoxaemia produced by the pulmonary shunt probably accounted for some of the exercise hyperpnoea, partly by increasing the chemoreceptor drive and partly by encouraging lacticacidaemia.5. Reduced arterial carbon dioxide tensions and bicarbonate concentrations had lowered the threshold and increased the sensitivity of the ventilatory response to

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