The effects of W7, a calmodulin (CaM)-inhibitor, and cyclic nucleotides on electrical coupling and uncoupling are studied in crayfish lateral giant axons (septate axons). The septate axons provide a relatively simple two cell system in which both surface membrane and junctional resistance can be measured independently. Four microelectrodes are inserted into a septate axon, two on each side of the septum. Hyperpolarizing current pulses (150 nA) are injected alternatively in the caudal and rostral axon segment and the resulting electrotonic potentials are recorded. The axons are uncoupled at regular intervals by superfusing them with acetate-containing saline solution (pH 6.3) in the presence or absence of W7 (50-100 microM) or, as a control, its nonchlorinated form (W5). W7 strongly inhibits the acetate-induced increased in junctional resistance, while W5 is ineffective. The uncoupling inhibition does not appear to be caused by an increase in cyclic nucleotide concentration, because in preliminary experiments exposure to db-cAMP or db-cGMP (up to 1 mM) does not seem to influence either the basic values of Rj or their changes with acetate. The data confirm previous evidence for a participation of CaM-like proteins in cell-to-cell channel gating.