The natural history of untreated proliferative sickle retinopathy (PSR) has been observed in 35 patients (40 eyes) with homozygous sickle cell (SS) disease and in 112 patients (114 eyes) with sickle cell-haemoglobin C (SC) disease over a mean follow-up period of 4.5 years (range 0.5-14.0 years). In both genotypes progression of PSR was most frequent between ages 20 and 39 years. Spontaneous regression was more common in SS disease (p = 0.01), and more likely to proceed to complete non-perfusion. In SC disease PSR tended to be stable in patients aged 40 and over, and non-perfused PSR lesions were significantly more likely to reperfuse (p = 0.01) than in SS disease. In both genotypes regression was not influenced by size or elevation of the PSR lesion. The tendency for PSR to regress in SS disease suggests that treatment is unnecessary in SS patients aged 40 and over.