The calcium-dependent modulation of type A K+ current (IA) has been investigated using a two-electrode voltage clamp on larval muscle cells of Drosophila. It was found that the amplitude of IA increases when [Ca2+]o is changed from 0.2 mM to 2 mM. The increase in IA amplitude is not due to overlap with the Ca(2+)-dependent fast K+ current, ICF, since it is observed also in slo1 mutants, which are deficient for this current. This effect is not due to Ca(2+)-dependent shifts in the steady-state activation/inactivation kinetics. The phenomenon is probably due to elevations in internal calcium since it is abolished by Ca2+ channel blockers and promoted by caffeine (5 mM) if added in the absence of external calcium. This calcium effect was dose-dependent since it was not observed in the presence caffeine plus 2 mM calcium in the bath nor for values of [Ca2+]o above 4 mM. The Ca(2+)-dependent modulation of IA is absent in V7, a mutation that causes overexpression of frequenin, a recoverin-like Ca(2+)-binding protein which stimulates guanylyl cyclase [31]. One possible explanation for the loss of IA modulation in the V7 mutation is that the excess of frequenin alters intracellular cGMP-dependent metabolic pathways responsible for the internal calcium homeostasis.