1. Residual endogenous insulin secretion can be assessed by the circulating C-peptide concentration and is present in up to 15% of subjects with established insulin-dependent diabetes mellitus (IDDM). Its role in lipid metabolism in IDDM is not clearly defined. We examined the relationships between serum lipid and lipoprotein concentrations and the response of circulating C-peptide to a test meal in 205 subjects with IDDM. 2. Lipid and lipoprotein levels and glycaemic control did not differ significantly between patients with undetectable, low or high C-peptide responses. 3. High density lipoprotein (HDL) cholesterol and its subfractions were inversely related to concentrations of serum triacylglycerols ( P < 0.01–0.001), but not to C-peptide or glycated haemoglobin (HbA,) levels. Levels of HbA, and triacylglycerols were correlated with one another ( P < 0.01). Analysis of variance revealed that differences in gender and triacylglycerol concentrations were the most important determinants of HDL and HDL 2 cholesterol levels. C-peptide only exerted a weak effect on HDL 2 cholesterol levels and no significant predictors of HDL 3 cholesterol were found. 4. It is concluded that endogenous insulin secretion (assessed by C-peptide concentration) is relatively unimportant in modifying HDL metabolism in IDDM and that associated clinical features, in particular ambient hypertriglyceridaemia, are of greater importance.