Genetically-manipulated mice harboring an α-myosin heavy chain Arg403Gln missense mutation (α-MHC 403/+ ) display a phenotype characteristic of familial hypertrophic cardiomyopathy (FHC). Male and female (30±8 week old) heterozygous α-MHC 403/+ mice and littermate controls were evaluated using a surface electrocardiogram (ECG) and an in vivo cardiac electrophysiology study (EPS). Wild type animals had normal intracardiac electrophysiology, with no significant differences between male and female control mice during EPS. The female wild-type mice did have slower heart rates and longer ECG intervals than their male wild-type counterparts. The female α-MHC 403/+ mice had similar ECG's, cardiac conduction times, and refractory periods compared with female wild-type mice. In contrast, male FHC mice had distinctive ECG and electrophysiologic abnormalities including right axis deviation, prolonged ventricular repolarization and prolonged sinus node recovery times. During programmed ventricular stimulation, 62% of male α-MHC 403/+ mice and 28% of female α-MHC 403/+ mice had inducible ventricular tachycardia. These studies identify gender-specific electrophysiologic abnormalities in α-MHC 403/+ FHC mice, concordant with the histological and hemodynamic derangements previously reported.