1. The effect of the cytosine- and guanine nucleotides on hypodynamic frog hearts was investigated. 2. After an ample discussion of our data and those of the literature we concluded: a) that for the positive inotropic effect (second phase) the polyphosphate structure of the nucleotides is important; that it is very probable that a phosphate liberation by rupture of energy rich phosphate bonds forms the base of the inotropic effect; that for the initial effect this phosphate liberation is potentiated by the —6 NH2 group in either the purine or the pyrimidine ring, while this configuration has no effect on the phosphate liberation in the second increase. Therefore it is likely that the initial and the second increase of cardiac contraction are based on two different processes of phosphate liberation; b) that the negative chronotropic effect of adenosine, AMP, ADP and ATP on the heart is based on the —6 NH2 group in the purine ring, which only has an effect if a ribose molecule is linked to the base.