Adipocyte insulin binding and insulin sensitivity to stimulation of lipogenesis were assessed in a group of extremely brittle diabetic patients who were resistant to subcutaneous insulin therapy and had required frequent and prolonged hospital admission. These patients had significantly lower maximum adipocyte insulin binding (1.78±0.18%) than age-, sex- and weight-matched stable diabetic control subjects (2.57±0.36%; p<0.05). Scatchard analysis suggested that the decreased binding was secondary to reduced receptor affinity with no change in receptor number. Adipocytes from the brittle subjects displayed resistance to insulin stimulation of lipogenesis compared with those from diabetic or normal control groups (half-maximal stimulation at 34±4, 15±3 and 13±2 pmol/l respectively; p<0.01 between brittle and stable diabetic groups). In the one subject who was treated with intraperitoneal insulin, the changes in insulin binding and sensitivity were found to have reverted towards normal. The peripheral tissue abnormalities of brittle diabetes may exacerbate the clinical syndrome although the relationship of these changes to the primary cause of the syndrome is uncertain.