Background: Leptin concentrations as a predictor of weight excess (WE) variations in obese children continue to be controversial. Aim and design: To evaluate the relationship between fasting leptin serum concentrations and the ability to maintain loss of WE during obesity treatment, 172 (82 males and 90 females) overweight children and adolescents (OW), 6-16 yr old, were recruited. The subjects were retrospectively selected among those who had demonstrated a reduction of their WE during an initial phase of 12 months of a WE reduction programme (WERP). Fasting serum levels of leptin were assayed, together with insulin, triacylglycerol and cholesterol, before (time 0) and at the end of the first phase of WERP (time 1), and BMI (Z-score) was determined at time 0, time 1 and at the end (time 2) of a subsequent second phase of 12 months. OW were subdivided according to wether their Z-BMI showed a persistent reduction also during the second phase (maintaining WE reduction subjects or MS) or showed a subsequent increase after the reduction observed during the first phase (relapsing WE subjects or RS). Results: A significant reduction in serum levels of leptin, insulin and lipids, paralleling Z-BMI reduction, was observed at the end of the first phase of WERP, during which we found a correlation between the decrease in serum leptin concentrations and the decrease in Z-BMI. The decrease in RS during the first phase ((DeltalgL(0-1)) was significantly greater when compared to that observed in MS (p<0.05). In two different multiple logistic regression analyses, where RS=0 and MS=1, serum leptin at time 1 [odds ratio (OR)=1.08; 95 % confidence interval (CI)=1.04-1.13] and DeltalgL(0-1) (OR=0.48; 95% CI=0.25-0.92), together with final pubertal stage (OR=0.78; 95% CI=0.63-0.96), were significantly associated with final subject status. Conclusions: Leptin serum levels after a previous WE reduction and its parallel decline are related to subsequent adiposity outcome. The lower the leptin serum concentration after previous WE reduction and/or the greater its decrease, the greater was the probability of WE relapse. (C) 2003, Editrice Kurtis.