The relative infrequency of renal stones in children is probably the main reason for the paucity of literature devoted to the study of urolithiasis in pediatric patients. Nonetheless, when pediatricians do address the issue, the contents of their papers reflect those prevalent in the adult literature; with one notable exception. Papers dealing with the potential role of urinary macromolecules in pediatric stone disease are very scarce indeed; to my knowledge, only four have been published in the English literature in the last 15 years. One of these is to be found in this issue and, like the remaining three, it compares the urinary excretion of glycosaminoglycans in healthy children and those with stones. This article briefly reviews the history of the association of urinary macromolecules, particularly glycosaminoglycans and proteins, with calcium oxalate urolithiasis, and discusses in more detail the published experimental evidence for their fulfilling a determinant role in stone formation.