Although prostacyclin (PGI2) has been shown to exert a protective effect on ischaemic hearts its precise mode of action remains obscure. Possible explanations include protection of the high energy phosphate stores (ATP and CP), maintenance of homeostasis with respect to Ca2+, and an antiaggregatory effect. The following experiments were undertaken to investigate these possibilities, using isolated, spontaneously beating rat hearts perfused with Krebs-Henseleit solution. Ischaemia was induced at 37 degrees C for 30 min by reducing the flow rate from 10.0 to 0.1 ml/min, and was followed by reperfusion. PGI2 was given as a constant infusion (20 ng/ml). The hearts were frozen and assayed for ATP and CP, or digested in HNO3 and assayed for Ca2+. Peak developed tension was recorded throughout. The results show that PGI2 slowed the rate of decline of developed tension during low flow perfusion, and hastened the recovery of contractions on reperfusion. These effects could not be accounted for in terms of an improved supply of ATP or CP, or an altered tissue Ca2+. The protective effect of PGI2 on isolated, buffer-perfused hearts may be a reflection of a generalized, but undefined, mechanism of cell preservation which has also been observed in other systems.