Context: It is unclear whether the relationship between 25-OHD and PTH is modulated by age or gender. Objective: To assess the 25-OHD-PTH relationship in 340 adolescents (10-17 years) and 443 elderly (65-85 years) of the same ethnic group, and living in the same sunny country. Assessments: Calcium intake was estimated. Serum calcium, phosphorus, 25-OHD and PTH were measured. Body fat was determined by DXA. Results: 25-OHD levels were lower in the elderly in the overall group (p<0.001) and within genders. 25-OHD levels were lower in females in the overall group and within age subgroups (p<0.05). PTH levels were higher in the elderly in the overall population and in both genders (p<0.001). There were no gender differences in PTH levels within age subgroups. For the same 25-OHD level, PTH levels were comparable across genders but were 1.5-2 folds higher in the elderly compared to adolescents (p<0.001). PTH correlated positively with age (p<0.001), body fat (p = 0.02), and negatively with calcium intake (p<0.001), and 25-OHD (p<0.001). The magnitude of the correlation with 25-OHD decreased after adjustment for age but not for gender. In multivariate analyses, age, 25-OHD and fat mass were independent predictors for PTH. In the elderly, after adjustment for serum creatinine, only 25-OHD and creatinine were independent predictors of PTH. Conclusion: The negative relationship between 25-OHD and PTH is modulated by age but not gender. Desirable 25-OHD levels derived from examining the 25-OHD-PTH relationship should therefore take into account the age of the population of interest. (C) 2010 Elsevier Inc. All rights reserved.