The stability of prostacyclin (PGI2) in whole blood and plasma was studied in vitro by measuring the disappearance rate of labeled prostacyclin during a 37 degrees C incubation. Prostacyclin was assayed using a quantitative chromatographic method. The half-life of PGI2 was 6.3 +/- 0.8 minutes (mean +/- s.d., n = 6) in citrated human whole blood, significantly shorter (p less than 0.001) than the 10.7 +/- 2.3 minute half-life in citrated human plasma (n = 7). Prior freezing and thawing of plasma did not affect the rate of PGI2 hydrolysis. These values, including the prolonged half-life in plasma, were similar in the blood (5.4 +/- 1.8 min, n = 7) and plasma (9.0 +/- 1.9 min, n = 14) of diabetic patients. In plasma samples from patients with thrombotic thrombocytopenic purpura, the half-life of prostacyclin (4.9 +/- 1.0 min, n = 4) was significantly shortened (p less than 0.001) compared to that in plasma from normal volunteers. The stability of prostacyclin in rabbit blood and plasma was also quantified. The PGI2 half-life in citrated rabbit plasma (10.8 +/- 1.1 min, n = 3) was similar to that in citrated human plasma from control subjects. In contrast to the findings in human blood, the half-life of PGI2 in citrated rabbit whole blood (11.7 +/- 3.3 min, n = 4) was not different from the rabbit plasma value. Substitution of EDTA for citrate did not affect the half-life in rabbit blood or plasma.