The relationship between insulin-like growth factor I (IGF I) and diabetic retinopathy was investigated. This somatomedin circulates bound to at least two large carrier proteins with molecular weights of approximately 150,000 and 35,000. Total and protein binding profiles of insulin-like growth factor I were determined in the serum of 18 patients who had had Type 1 (insulin-dependent) diabetes for 15-20 years, but had no signs of nephropathy and a similar degree of mild subclinical neuropathy. Nine had preproliferative or proliferative retinopathy and 9 had little or no background retinopathy but there was no difference in diabetes duration, insulin doses or glycaemic control between the two groups. In the latter group, the amounts of the somatomedin I and the serum profiles were similar to those in 9 healthy control subjects. In patients with advanced retinopathy, however, binding of insulin-like growth factor I to the carrier proteins was significantly altered. Binding to the low molecular weight protein increased to 140% whereas binding to the large molecular weight protein decreased to 70% of the normal level. In the latter Type 1 diabetic patients total serum insulin-like growth factor I was decreased to 60% of the normal level (p less than 0.02). When the alteration in serum profile was adjusted for, the level of somatomedin associated with the small carrier complex was normal whereas that associated with the large carrier complex was reduced by almost 60% in Type 1 diabetic patients with retinopathy. It is proposed that the total circulating somatomedin level is low in advanced diabetic retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)