Underlying mechanisms of drug-induced long QT syndrome are not fully understood. Our objective was to evaluate gender-related differences for block of the rapid (IKr) or/and the slow (IKs) components of the delayed rectifier potassium current in prepubertal male and female guinea pigs (n = 120) treated with or without verapamil. Indapamide (IKsblocker) prolonged the monophasic action potential duration at 90% repolarisation (MAPD90) in females more than in males (15.1 + 0.5 vs 9.7 + 1.3 msec; P < .05) in verapamil treated animals. In contrast, MAPD90prolongation induced by domperidone or dofetilide (IKrblockers) was not different between genders. Verapamil treatment augmented prolongation of MAPD90caused by dofetilide or domperidone (P < .01). In conclusion, 1) females exhibited greater prolongation of MAPD90when exposed to indapamide, 2) no gender-related differences were observed for IKrblockers, and 3) verapamil treatment did not uncover gender-related differences in IKror IKsblock, although it augmented prolongation of cardiac repolarization by IKrblockers.