The effects of excitability-inducing materials (EIM) and electrical stimulation on Ca+(+)-induced Ca++ release were studied in this experiment. Direct application of three EIM (bacterial EIM, alamethicin, Nal) did not release Ca++ from skinned rat cardiac fibers or from an SR suspension. Direct electrical stimulation of the SR suspension had no effect on Ca++ release either. However, both electrical stimulation and pre-treatment with an EIM augmented Ca+(+)-induced Ca++ release in the skinned fiber and led to increased contractility of the fiber in a dose-dependent manner. When electrical stimulation and EIM application were superimposed, their effects were additive, suggesting that information transfer across the junction between T-tubule and SR is at least chemical in nature.