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The adipocyte-derived hormone, leptin, has been implicated in the regulation of appetite, weight gain and glucose homeostasis as well as in liver fibrogenesis, hematopoiesis and immune function. No previous reports have clearly defined pathologically elevated or decreased serum leptin levels for Caucasian adults. The aim of this study was to define and characterize subjects with relative hyper- and hypoleptinemia in a large population-based German cohort. Percentiles of leptin levels by body mass index (BMI) were calculated from 4971 adult Germans, and the participants with leptin levels above the 95th and below the 5th percentile were defined as relatively hyperleptinemic and relatively hypoleptinemic, respectively, for their BMI. These participants were compared with the intermediate group with respect to anthropometric and clinical data and parameters of glucose and iron metabolism, lipid status, renal, adrenal and reproductive function. Relatively hyperleptinemic participants (HL) showed higher insulin, c-peptide, and total cholesterol levels than the hypoleptinemic subjects; in males, ferritin levels were higher and testosterone levels lower in the HL group. In conclusion, we report the first percentile curves for serum leptin by BMI in a large Caucasian population. Relatively low leptin values may be associated with a lower metabolic risk than relatively high serum leptin values.