Factor-VIII-Related antigen (VIII R:Ag) is known to be produced by the blood vessel wall. Noxious stimuli increase endothelial release of VIII R:Ag. It might be expected that the development of vasculitis would be associated with increased levels of VIII R:Ag. To investigate this, eight different groups of subjects were studied: 25 patients with systemic sclerosis, 19 with systemic lupus erythematosus, 15 with rheumatoid arthritis (RA) plus vasculitis, 19 with systemic vasculitis and 14 with atherosclerosis. These groups were compared to 29 patients with primary Raynaud's disease, 15 with RA without vasculitis and 50 controls. Results showed that where there was evidence of vascular disease, then VIII R:Ag was elevated. VIII R:Ag appeared to be a more specific marker for vascular damage than erythrocyte sedimentation rate or C-reactive protein. Longitudinal studies in 11 patients showed good correlation between progression of vascular disease and VIII R:Ag.