OBJECTIVE: To-examine the interrelationship of circulating leptin concentrations, basal metabolic rates (BMR) and respiratory quotients (RQ) in young and older adults. DESIGN: Cross sectional study. SUBJECTS: Seventy-six Australian men and women, 48 young (< 35 y) and 28 older ( > or = 50 y). MEASUREMENTS: Fasting plasma leptin concentrations by RIA, BMR and RQ by indirect calorimetry, percentage body fat (BF%), fat mass (FM) and fat-free mass (FFM) from total body water (TBW) based on deuterium dilution, waist and hip circumferences from anthropometry. RESULTS: Older subjects had significantly higher BF%, FM and waist-to-hip ratio (WHR), but significantly lower FFM and absolute BMR as compared to younger subjects. Absolute leptin concentrations were 60% higher in older subjects but did not achieve statistical significance. There was, however, a significant gender x age group interaction in leptin concentrations. This was reflected in a significant inverse relationship between age group and leptin in women when data was controlled for waist circumference (r = -0.38, P = 0.028), or FM (r = -0.36, P = 0.042). A similar relationship was not observed in men on controlling for BF% or FM. Log transformed plasma leptin was best explained by a model that included BF%, gender, age-group, gender x age-group and WHR r = 0.75, adjusted r2 = 0.56, standard error of estimate (SEE) = 0.73 ng/ml). BMR was best explained by FFM, FM and age group r = 0.94, adjusted r2 = 0.87; SEE = 429 kJ/day). On controlling for BF%, WHR and FFM, leptin was negatively related to RQ only in older men (r = -0.67, P = 0.033). There was no relationship of leptin to BMR in the groups studied. CONCLUSION: The study demonstrates an age-related modification of the gender bias in leptin, and a gender-specific inverse relationship between leptin and RQ in older people. The decline in leptin and the lack of a relationship between RQ and leptin in older women may indicate an increased risk of weight gain relative to older men.