Adhesion molecules enabling leukocytes to communicate and adhere are essential for immunological and inflammatory responses. Circulating forms of these adhesion molecules are detected, although their influence on immunological functions is unknown. We have measured soluble levels of E-selectin, vascular adhesion molecules-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in sera from 65 HIV-1-seropositive patients and controls. We found significantly higher levels of soluble VCAM-1 (sVCAM-1) and ICAM-1 (sICAM-1) in both symptomatic and asymptomatic HIV-1-infected patients than in controls (P <0.01). Both sICAM-1 and sVCAM-1 correlated to serum levels of neopterin (r = 0.40, P < 0.001; r = 0.46, P <0.001, respectively) and TNFalpha (r = 0.44, P < 0.01; r = 0.49, P < 0.001, respectively), while only sVCAM-1 correlated strongly to CD4+ lymphocyte count (r = -0.46, P < 0.001). Patients infected with Mycobacterium avium intracellular complex had significantly higher levels of sVCAM-1 and sICAM-1 than other AIDS patients (P < 0.05), while patients with cytomegalovirus disease had significantly lower levels both of sE-selectin and sICAM-1 (P < 0.05) than other AIDS patients. In conclusion, we found abnormal levels of circulating adhesion molecules in both symptomatic and asymptomatic HIV-1 infection including AIDS. The correlation to other parameters and clinical events may implicate involvement of circulating adhesion molecules in the immunopathogenesis of HIV-1 infection.