We have shown previously that verapamil reduces the slope of the action potential duration (APD) restitution relation, suppresses APD alternans and converts ventricular fibrillation (VF) into a periodic rhythm. To determine whether these effects result primarily from reduction of the APD restitution slope, as opposed to alteration of calcium dynamics unrelated to restitution, we tested the effects of hypocalcemia ([CaCl2]=31-125 microM) in canine ventricle. At normal [CaCl2] (2.0 mM), the slope of the APD restitution relation was >1, APD alternans occurred during rapid pacing and VF was inducible. During hypocalcemia the slope of the restitution relation remained >1 and the magnitude of APD alternans was unchanged. VF still was inducible and the mean cycle length and the variance of the FFT spectra during VF were not altered significantly. These results suggest that reduction of APD restitution slope, rather than blockade of ICa per se, is responsible for the antifibrillatory effects of verapamil in this model of pacing-induced VF, lending further support to the idea that APD restitution kinetics is a key determinant of VF.