Neonatal diabetes mellitus--defined here as hyperglycemia occurring within the first month of life that lasts for at least two weeks and requires insulin therapy--is a very rare form of the disease. Little is known about it, particularly with respect to its long-term course. We studied two brothers who had neonatal diabetes and obtained follow-up information on 34 patients described in the literature as well as information on 21 additional patients. Forty-seven of the patients had neonatal diabetes, as defined above, and in 10 others the onset was between the first and third month of life. Twenty-six of the 57 infants had permanent diabetes, 18 had transient diabetes, and 13 had transient diabetes that recurred when they were 7 to 20 years old. Neonatal diabetes was associated with the Wolcott-Rallison syndrome in six infants, hyperuricemia due to phosphoribosyl-ATP pyrophosphatase hyperactivity in two, and celiac disease in two. Forty-one of 45 neonates in whom the duration of gestation and birth weight were known were small for their gestational ages. There were two pairs of affected twins and four other families with two or more infants with neonatal diabetes, but only three parents had diabetes. The incidence of neonatal diabetes mellitus in Germany has been estimated to be 1 in 500,000 neonates. Neonatal diabetes differs from insulin-dependent diabetes in that its course is highly variable. Some patients have permanent diabetes, but others have transient or lasting remissions.