BACKGROUND: Macrovascular disease in diabetes mellitus is a multifactorial process resulting in part from accelerated atherosclerosis and increased thrombosis. The resultant cardiovascular mortality is up to five times that of an age-matched non-diabetic population. Recently, cell adhesion molecules (CAMs) have been demonstrated in atherosclerotic plaques and implicated in the initiation and development of atherosclerosis. METHODS: To assess circulating CAMs as potential predictors of the development of macrovascular disease in diabetes mellitus, we carried out a 5-year prospective study in 28 diabetic patients without manifest macrovascular disease at entry. Circulating CAMs [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin and E-selectin] were measured at baseline and at follow-up. RESULTS: Except for neuropathy, no patient had other microvascular diabetic complications (retinopathy or nephropathy) or clinically manifest macrovascular disease. Eleven patients developed macrovascular disease at follow-up (seven coronary heart disease, two cerebrovascular disease, two peripheral vascular disease). At baseline, systolic blood pressure and serum creatinine were higher (but within normal range) in patients developing macrovascular disease. Baseline ICAM-1 was significantly higher in the patients who developed macrovascular disease than in those who did not, and it remained so even after adjusting for age, systolic blood pressure, creatinine and glycaemic control (P=0.0007). However, baseline VCAM-1, P-selectin and E-selectin were not found to be associated with macrovascular disease. The risk of developing macrovascular disease was associated with increasing baseline concentrations of ICAM-1 [odds ratios 1.04 (95% CI 1.01-1.07); P=0.01]. No correlation was seen between ICAM-1, HbA(1) and cholesterol. CONCLUSION: This study suggests that ICAM-1 may predict development of macrovascular disease in diabetes mellitus.