The pathogenesis of autoimmune insulin-dependent (Type 1) diabetes mellitus (IDDM) is far from being resolved, despite extensive genetic and immunological research. However, recent experimental data from immune and endocrine studies using spontaneous or transgenic models of the disease have emphasized the role of the islet of Langerhans, and particularly beta cells, in IDDM pathogenesis. Part I of this review (Diabetes Metab, 1997, 23, 181-194) considered the various ways normal beta cells cope with increased demands on their resources in different models of hyperglycaemia in order to provide a better delineation and comparison of the mechanisms implicating these cells in the pathogenesis of IDDM and non-insulin-dependent (Type 2) diabetes mellitus (NIDDM). Part II attempts to improve our understanding of the various mechanisms through which beta cells, and perhaps the entire islet of Langerhans, may influence the immune system from the perinatal period to adulthood. Genetics and beta-cell behaviour are considered during prediabetes in human and experimental models of IDDM and NIDDM. Attention is focused on the spontaneous model of the disease, the non-obese diabetic (NOD) mouse, which in addition to providing genetic data, appears to be useful for sequential study of the early developmental, immune and endocrine events that occur in IDDM pathophysiology.