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It has been suggested that King George III of Great Britain suffered from the haem biosynthetic disorder, variegate porphyria. This diagnosis is pervasive throughout the scientific and popular literature, and is often referred to as the ‘Royal Malady.’ The authors believe it inappropriate to view the case for porphyria purely in terms of symptoms, as has generally been the case in his presumptive acute porphyria diagnosis. Accordingly, this review provides a current description of the natural history and clinical presentation of the porphyrias, against which we measure the case for porphyria in George III and his relatives. The authors have critically assessed the prevalence of porphyria in a population, the expected patterns and frequency of inheritance, its penetrance and its expected natural history in affected individuals, and conclude that neither George nor his relatives had porphyria, based on four principal reasons. First, the rarity of the disease mandates a very low prior probability, and therefore implies a vanishingly low positive predictive value for any diagnostic indicator of low specificity, such as a historical reading of the symptoms. Second, penetrance of this autosomal dominant disorder is approximately 40%, and one may expect to have identified characteristic clinical features of porphyria in a large number of descendants without difficulty. Third, the symptoms of both George III and his relatives are highly atypical for porphyria and are more appropriately explained by other much commoner conditions. Finally, the natural history of the illnesses reported in this family is as atypical for variegate porphyria as are their symptoms.