This study included all patients, with known HIV-1 status, admitted to hospital over a 5-year period with serum ferritin values exceeding 1500 μg/l. Markedly elevated serum ferritin levels are associated with a host of causes which poses a diagnostic dilemma, as the aetiology is often highly dependent on local epidemiology. We evaluated patients' records retrospectively to determine underlying causes of possible hyperferritinaemia. Aetiologies associated with hyperferritinaemia varied significantly depending on HIV-1 status. In patients infected with the HIV-1 virus, infectious causes predominated with Mycobacterium tuberculosis accounting for more than 50% of the patient population with an odds ratio of 17·98 (95% confidence interval 8·31–38·88) in HIV-positive compared to HIV-negative patients. Of the HIV-1-negative patients, hereditary haemochromatosis accounted for less than 2% of patients and chronic renal failure was the most common diagnosis. The finding of hyperferritinaemia should prompt determination of HIV-1 status, as this impacts significantly on aetiological epidemiology. In HIV-1-positive patients, aggressive investigation for mycobacterial infection should be undertaken in cases of combined hyperferritinaemia and positive HIV-1 serology.