Adult women have longer QT intervals compared with men of a similar age, indicating differences in the speed of repolarisation of the ventricles. We investigate the influences of gender on ventricular electrophysiology and intracellular Ca2+ regulation of the guinea pig heart. Comparing sexually mature animals, females exhibited a significantly longer APD. Peak L-type Ca2+ current (ICaL) was larger in females and when this current was inhibited with nifedipine the gender differences in APD were removed. APD differences also disappeared when the SR was depleted of Ca2+. Inactivation of ICaL during a clamp step is faster in females but slower during an action potential and SR Ca2+ content is larger. We suggest that gender differences in APD result from variation in the kinetics of ICaL stemming from alterations to Ca2+ release. (C) 2009 Elsevier Inc. All rights reserved.