Iontophoretic injection of Ca2+ causes reduction of I0A (an early rapidly activating and inactivating K+ current) and I0C (a late Ca2+-dependent K+ current) measured across the isolated type B soma membrane (Alkon et al., 1984, 1985; Alkon and Sakakibara, 1984, 1985). Similarly, voltage-clamp conditions which cause elevation of [Ca2+]i are followed by reduction of I0A and I0C lasting 1-3 min. Iontophoretic injection of highly purified Ca2+/CaM-dependent protein kinase II (CaM kinase II) isolated from brain tissue (Goldenring et al., 1983) enhanced and prolonged this Ca2+-mediated reduction of I0A and I0C. ICa2+, a voltage-dependent Ca2+ current, also showed some persistent reduction under these conditions. Iontophoretic injection of heat-inactivated enzyme had no effect. Agents that inhibit or block Ca2+/CaM-dependent phosphorylation produced increased I0A and I0C amplitudes and prevented the effects of CaM kinase II injection. The results reported here and in other studies implicate Ca2+-stimulated phosphorylation in the regulation of type B soma ionic currents.