The effect of creatinol-O-phosphate (N-methyl-N-(beta-hydroxyethyl)guanidine O-phosphate, creatinolfosfate, Aplodan) pretreatment has been studied on the recovery of contractility of rat isolated heart after hypoxia or ischemia. In normoxia creatinol-O-phosphate (100 mumol/l) evoked a positive inotropic effect only when glucose was present in the physiological solution, it also evoked a slight negative chronotropic effect that was independent of glucose. When creatinol-O-phosphate was present during hypoxia, in the physiological solution, the recovery of the contraction after reoxygenation (in the absence of the drug) was improved in a dose-dependent manner. When creatinol-O-phosphate was present in the physiological solution before ischemia, the recovery of the contractility after reperfusion was higher than in controls; the presence of creatinol-O-phosphate during reperfusion after ischemia accelerated the recovery of contractility. The action of creatinol-O-phosphate on the recovery of cardiac contractility after ischemia was also observed in hearts partially protected with a cardioplegic solution. It is suggested that creatinol-O-phosphate could exert its cardioprotective effect by an action on anaerobic glycolysis.