Recently, extremely high concentrations of endothelin-1 (ET-1) were detected in the pericardial fluid of patients undergoing cardiac surgery. This study was designed to characterize ET-1 levels in plasma and pericardial fluid of dogs. Plasma and pericardial fluid samples were extracted using SepPak C18 cartridges and ET-1 levels were measured by a specific radioimmunoassay. Pericardial fluid ET-1 levels (739 +/- 81 pg/ml; n = 10) were significantly higher than respective plasma levels (22.4 +/- 4.0 pg/ml; p < 0.05). The mean pericardial fluid: plasma ratio of ir-ET-1 concentration was 54.7 +/- 16.8. In HPLC analysis, the total ET-1-like immunoreactivity of pericardial fluid co-eluted with ET-1 standard. In anesthetized dogs (n = 6), disappearance of [125I]ET-1 was sixfold slower in the pericardial space than in plasma. Our results show that high concentrations of ir-ET-1 can be found in canine pericardial fluid. Slow elimination of ET-1 from the pericardial fluid compartment may contribute to high peptide levels.