Specimens removed at parathyroidectomy from 41 patients with chronic renal failure, 12 patients with parathyroid adenomas and parathyroid glands from 24 autopsies were studied by light microscopy, immunohistochemistry and electron microscopy. The morphological abnormalities were correlated with clinical data obtained from patients' medical records. Glandular enlargement in chronic renal failure, primarily due to parenchymal cell hyperplasia, was as much as 20 times the normal in contrast to 40 times the normal cases of adenomas. Glandular hyperplasia was mostly due to an increase in the number of chief cells and to a lesser extent increase in the number of oxyphil cells, transitional oxyphil cells and water-clear cells. There was a corresponding reduction in fat and intracellular lipid content. There were differences in the overall morphology of normal, hyperplastic and adenomatous glands. The clear histological distinction between hyperplastic and adenomatous glands was at times difficult. There was no correlation between the extent of hyperplasia, the cause of renal failure, duration of chronic renal failure, levels of serum calcium, phosphate or parathyroid hormone. Immunohistochemical studies showed that all 3 types of cells contained parathyroid hormone but in hyperplastic and adenomatous glands there was a reduction in parathyroid hormone and chromogranin A staining. There were no specific ultrastructural abnormalities which would distinguish between hyperplastic and adenomatous glands.