Vascular or humoral rejection (as defined by linear deposits of immunoglobulin and complement in myocardial capillaries) and the presence of circulating lymphocytotoxic anti-HLA antibodies are each associated with reduced long-term graft or patient survival. The relationship between these two factors has not been determined. We used immunofluorescent techniques to study 46 cardiac biopsy specimens in 16 patients from 15 to 412 days after transplantation. Biopsy specimens were selected from the first 2 months, and at approximately 6 and 12 months after transplantation and did not include episodes of acute cellular rejection. Each specimen studied was compared to a serum sample drawn an average of 1.8 days (range, 0 to 9 days) from the time of biopsy to assay for circulating anti-HLA antibodies. Of the specimens obtained at or near a positive anti-HLA antibody test, 90% (27 of 30) were found to have linear deposits of immunoglobulin (not necessarily with complement) versus 75% (12 of 16) of specimens obtained at the time of a negative test. Twenty-one cases of vascular rejection were documented. Both immunoglobulin M and immunoglobulin G were deposited along with complement in 13 instances; immunoglobulin M and complement were deposited in eight cases; no case had only immunoglobulin G and complement. The presence of circulating anti-HLA antibody in the serum was associated with 14 of the 21 cases of vascular rejection. Linear deposits of immunoglobulin in the capillaries of myocardium were frequently observed when anti-HLA antibodies were present in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)