We have quantified levels of CD105, its ligand TGFbeta and receptor-ligand complexes in sera from healthy individuals (n=31), patients with triple vessel disease documented by coronary angiography (TVD; n=36) and patients with chest pain and a positive exercise electrocardiogram but with normal coronary angiogram (NCA; n=30). Both active TGFbeta1 and active plus acid-activatable TGFbeta1 [(a+l)TGFbeta1] were significantly depressed in patients with TVD compared with the other two groups (P</=0.04). CD105 levels in TVD patients were also diminished but elevated in NCA patients. In contrast, patients with TVD had more CD105/TGFbeta1 complex in their sera than the other two groups, suggesting that this may be the reason why TVD patients had low levels of receptor and ligand. TGFbeta3 levels were similar in the three groups, but elevated CD105/TGFbeta3 levels were noted in patients with NCA compared with those with TVD and healthy individuals (P< or =0.02). CD105 was correlated with both active TGFbeta1 and (a+l)TGFbeta1 (P=0.02). CD105 also strongly correlated with TGFbeta3 and CD105/TGFbeta3 complexes (P=0.001 in both cases). The changes in levels of CD105, TGFbeta1 and the receptor-ligand complexes in sera of patients with atherosclerosis suggest that these molecules may be important in the pathobiology of the atherosclerotic disease. Further studies on sequential samples from a larger cohort of patients are needed to define a causal relationship between these molecules and the disease progression.