The etiology of malnutrition-related diabetes mellitus (MRDM) -- protein-deficient pancreatic diabetes (PDPD) and fibro-calculous pancreatic diabetes (FCPD) -- is unclear. We studied the role of autoimmunity against pancreatic islet cells in the etiology of these two subtypes of MRDM by measuring islet-cell antibodies (ICA) in 23 patients with PDPD, 25 with FCPD and 62 with Type 1 diabetes. Three patients (13%) with PDPD had detectable ICA, including a patient with a high titre of ICA (> 80 JDF units). The frequency of ICA in patients with PDPD was significantly lower than subjects with Type 1 diabetes 2262, 35%; P < 0.05). Among patients studied at onset, ICA prevalence was lower in the PDPD patients (17, 14%) compared to subjects with Type 1 diabetes (820, 40%). No patient of FCPD had detectable ICA (P < 0.001 vs. Type 1 diabetes subjects). We conclude that autoimmunity may play a role in the etiology of some patients with the PDPD subtype of MRDM. However, FCPD is unlikely to have an autoimmune etiology.