Adiponectin, an adipocyte-specific secretory protein known to induce apoptosis, has been reported to be inversely related to breast and endometrial cancers and recently found to inhibit proliferation of myeloid but not lymphoid cell lines. We hypothesised that adiponectin may be inversely associated with acute myeloblastic leukaemia (AML), but not with acute lymphoblastic leukaemia of B (ALL-B) or T (ALL-T) cell origin in children. Blood samples and clinical information were collected over the period 1996-2000 from 201 children (0-14 years old) with leukaemia (22 AML, 161 ALL-B and 18 ALL-T cases) through a national network of childhood Hematology-Oncology units in Greece and from 201 controls hospitalised for minor pediatric ailments. Serum adiponectin levels were measured under code, at the Beth Israel Deaconess Medical Center, Boston, MA, USA using a radioimmunoassay procedure. Each of the three leukaemia groups was compared with the control group through multiple logistic regression. Odds ratios (OR) and 95% confidence intervals (95% CI) for an increase of adiponectin equal to 1 s.d. among controls were estimated controlling for gender, age, as well as for height and weight, expressed in age-gender-specific centiles of Greek growth curves. Adiponectin was inversely associated with AML (OR=0.56; 95% CI, 0.34-0.94), whereas it was not significantly associated with either ALL-B (OR=0.88; 95% CI, 0.71-1.10) or ALL-T (OR=1.08; 95% CI, 0.67-1.72). Biological plausibility and empirical evidence point to the importance of this hormone in the pathogenesis of childhood AML.