Aims: To evaluate whether clinically relevant concentrations of stimulated C-peptide in response to a mixed-meal tolerance test can be detected after almost 30 years of diabetes in people included in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. Methods: Mixed-meal tolerance tests were performed in a sample of 58 people. C-peptide levels were measured using a chemiluminescent immunoassay. This sample size assured a high probability of detecting C-peptide response if the true prevalence was at least 5%, a level that would justify the subsequent assessment of C-peptide in the entire cohort. Results: Of the 58 participants, 17% showed a definite response, defined as one or more post-stimulus concentrations of C-peptide > 0.03 nmol/l, and measurable concentrations were found in all participants. Conclusions: These results show that a stimulated C-peptide response can be measured in some people with long-term Type 1 diabetes. Further investigation of all participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study will help relate long-term residual C-peptide response to glycaemia over time and provide insight into the relevance of this response in terms of insulin dose, severe hypoglycaemia, retinopathy, nephropathy and macrovascular disease. Establishing the clinical relevance of long-term C-peptide responses is important in understanding the impact that therapy to preserve or improve b-cell function may have in patients with long-term Type 1 diabetes.