Ten patients with systemic vasculitis, all positive for anti-neutrophil cytoplasm antibody (ANCA), were followed for a mean of 36 weeks to determine the prevalence of anti-endothelial cell antibodies (AECAs) and the relationship between AECAs, ANCAs, and disease activity. Anti-endothelial cell antibodies were detected in eight (80%) patients at some time during the study. The levels of both AECAs and ANCAs changed with time, and these autoantibodies were present in 48% and 63% of the total 100 serum samples, respectively. Eighteen clinical remissions were observed; in 16 (88.9%) cases the level of ANCAs dropped. Fifteen (83.3%) of the 18 remissions were among the AECA-positive patients and the level of AECAs decreased in 13 (86.7%) instances (P = not significant). There were 11 episodes of disease relapse; all were associated with an increase in the level of ANCAs. Nine (81.8%) of the 11 relapses were among AECA-positive patients, and the level of AECAs increased in eight (88.9%) cases (P = not significant). Serum levels of AECAs appeared less suppressible by cyclophosphamide therapy compared with ANCAs, and patients who were persistently positive for AECAs despite being ANCA-negative during remissions were at risk of subsequent relapse. Disease recrudescense was not observed in patients persistently tested negative for both AECAs and ANCAs. Intravenous immunoglobulin therapy was used in four patients and resulted in clinical improvement in all cases, but with variable changes in the levels of AECAs and ANCAs. We conclude that AECAs are commonly detected in patients with systemic vasculitis and their levels show a relationship to disease activity similar to that for ANCAs.(ABSTRACT TRUNCATED AT 250 WORDS)