1. Obesity is known to increase the risk for atherosclerotic diseases. Serum levels of cellular adhesion molecules are reported to be indices of atherosclerosis. The aim of the present study was to assess the effect of weight reduction on soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin). 2. Eighteen non-diabetic normotensive obese women participated in a 3 month lifestyle-modification programme (intervention group). The programme consisted of lectures on diet, exercise sessions and behavioural modification by weight charting. Fourteen women who did not enter the programme served as controls. Body fat mass (FM) was measured by dual-energy X-ray absorptiometry. Soluble ICAM-1 and sE-selectin were measured by ELISA. 3. After 3 months, sICAM-1 and sE-selectin, as well as body FM, decreased in the intervention group (P < 0.001), while no changes were observed in the control group. The baseline sE-selectin was positively correlated with total body FM, trunk FM and percentage body fat (r = 0.50-0.57; P < 0.01), but not with leg FM. The change in sE-selectin was also correlated with changes in total body FM and trunk FM (both r = 0.46; P < 0.01). Baseline sICAM-1 was not significantly correlated with these variables. The associations between changes in sICAM-1 and changes in total body FM or trunk FM were of borderline significance (both r = 0.34; P = 0.06). Linear regression analysis indicated that the change in sE-selectin was explained by the change in trunk FM (R2 = 0.18; P < 0.01). 4. Soluble ICAM-1 and sE-selectin were positively correlated with obesity, especially with central obesity. Weight reduction resulted in decreases in soluble adhesion molecules, which may suggest a downregulation of endothelial activation.