20 out of 179 diabetics treated with oral hypoglycaemic agents (O.H.A.) within 3 mo of diagnosis had pancreatic-islet-cell antibodies (ICAb) in their sera at diagnosis or later. 13 of these 20, compared with only 14 of the remaining 159, subsequently required insulin at a mean follow-up of 2 yr 10 mo and 4 yr 11 mo, respectively (p less than 10(-7)). 5 of the 7 ICAb-positive diabetics still continuing on O.H.A. therapy after a mean follow-up of 4 yr 6 mo required maximum or near-maximum combined oral therapy, while only 34 of the 145 ICAb-negative diabetics continuing on O.H.A. did so at a mean follow-up of 5 yr 4 mo (p less than 0.02). In addition, 81 diabetics treated initially with diet for a mean time of 4 yr 7 mo before going on to O.H.A. therapy were studied. All were ICAb-negative when tested at a mean interval of 6 yr 10 mo from diagnosis. By the end of the mean follow-up period of 10 yr 3 mo, 27 were on combined oral therapy and 3 had been transferred to insulin treatment. ICAb-positive diabetics on O.H.A. had a high prevalence of a personal history of organ-specific autoimmune disease, thyrogastric antibodies, a family history of insulin-dependent diabetes and possibly of HLA-B8 comparable to that in insulin-dependent diabetes and higher than that expected in a control population or in diabetics controlled by diet alone. We believe that ICAb-positive diabetes controlled by O.H.A. is an earlier stage in the same disease process (type-I diabetes) that culminates in insulin-dependency.