In order to investigate the effect of intracellular cyclic GMP on calcium current the whole-cell patch clamp technique with internal perfusion method was used in isolated ventricular myocytes of the rabbit. Cyclic GMP, 8-bromo-cyclic GMP, cyclic AMP, isoprenaline and forskolin were perfused into cells and their effects on calcium current were analysed by applying depolarizing step pulses of + 10 mV in amplitude far 300 msec from holding potential of - 40 mV. Not only cyclic AMP (100 μM) but also cyclic GMF (100 μM) increased the basal calcium current. 8-Bromo-cyclic GMP (100 μM), a good stimulator of the cyclic GMP-dependent protein kinase, also increased the basal calcium current and its peak amplitude of calcium current was larger than that in the presence of cyclic AMP or cyclic GMP alone. In the presence of 100 μM cyclic GMP or 100 μM 8-bromo-cyclic GMP, already augmented calcium current was potentiated by intracellular application of 100 μM cyclic AMP or 1 μM isoprenaline or 1 μM forskolin. In the presence of cyclic GMP, acetylcholine reduced the calcium current only when the calcium current was increased by isoprenaline. From the above results it could be concluded that intracellular perfusion with cyclic GMP increases the basal calcium current via a mechanism involving a cyclic GMP-dependent protein kinase.