[125I]Insulin binding to monocytes (36 diabetics) and erythrocytes (11 diabetics) from newly discovered insulindependent diabetics was measured before treatment and during the first 6 months of insulin and diet therapy. At the onset of diabetes, the tracer [125I]insulin binding to monocytes showed great heterogeneity, with the distribution of binding values being significantly different from that of healthy controls (P<0.01). In an attempt to examine if the insulin receptor reactivity at the onset of insulin-dependent diabetes might be genetically controlled, complete HLA-ABC and HLA-DR typings were performed. However, no significant relationships were detected between monocyte insulin binding and HLA antigens. The longitudinal studies showed that the patients who initially had higher monocyte insulin binding than the mean of healthy controls (high binders) exhibited a significant decrease in insulin binding during 10 days of treatment, whereas those with initially decreased monocyte insulin binding (low ...