Cardiac arrhythmias cause sudden death in 300,000 United States citizens every year. In this study, we describe two new loci for an inherited cardiac arrhythmia, long QT syndrome (LQT). In 1991 we reported linkage of LQT to chromosome 11p15.5. In this study we demonstrate further linkage to D7S483 in nine families with a combined lod score of 19.41 and to D3S1100 in three families with a combined score of 6.72. These findings localize major LQT genes to chromosomes 7q35-36 and 3p21-24, respectively. Linkage to any known locus was excluded in three families indicating that additional heterogeneity exists. Proteins encoded by different LQT genes may interact to modulate cardiac repolarization and arrhythmia risk.