AIMS: To investigate the influence of a family history of Type 2 diabetes mellitus (T2DM) on resting heart rate variability in the absence of concomitant metabolic disorders. METHODS: We studied 55 first-degree relatives (FDRs) of subjects with T2DM and 36 control subjects without any known family history of diabetes. FDRs were recruited from a University Hospital out-patient diabetes clinic. The protocol included: oral glucose tolerance test (30, 60, 90 and 120 min after ingestion of 75 g glucose) blood glucose, plasma insulin, cholesterol and subfractions, triglycerides, leptin and C-reactive protein. Heart rate variability (HRV) at rest was determined by spectral analysis of interbeat intervals recorded during 10 min in the supine position. RESULTS: HRV was lower in FDRs compared with control subjects (P < 0.05). Multiple regression analysis identified cholesterol (P = 0.014) and triglycerides (P = 0.014) as significant independent predictors (model r = 0.40; P < 0.001) of HRV. Since FDRs had higher values for anthropometric and metabolic variables known to alter HRV, we performed an ancova adjusted for cholesterol and triglycerides and also another analysis in which the groups were comparable for anthropometric and metabolic characteristics. Comparison of FDRs and comparable control subjects revealed no significant difference in HRV (P > 0.05). CONCLUSIONS: A family history of T2DM, in the absence of concomitant metabolic disorders, does not impair heart rate variability.