Several islet antigens have been shown to modify the time of onset and severity of spontaneous insulin dependent diabetes mellitus (IDDM) in NOD (non-obese diabetic) mice. Oral, intravenous and intra-nasal administration of insulin and glutamic acid decarboxylase (GAD) or their derived peptides have all been shown to be effective to differing degrees in reducing the incidence and delaying the onset of diabetes in this mouse model of the disease. Incomplete Freund's Adjuvant (IFA) has also played a key role in tolerance when co-administered with insulin peptides subcutaneously. We show that route of administration may be of crucial importance, since although insulin B chain and the B9-23 peptide given in IFA subcutaneously protected (either partially or completely) from IDDM, when given intraperitoneally they completely failed to modify the disease.