The present study examined the contribution of genetic factors to Digit Symbol performance and its decline in 23 monozygotic twin pairs (mean age at examination 1, 57.1 years) and 21 dizygotic twin pairs (mean age at examination 1, 56.3 years). These men were assessed twice during a 5-year interval as part of the National Heart, Lung, and Blood Institute Twin Study. The prevalence of decline (a change, greater than 1 SD) during the 5-year interval was 35% and 39% for monozygotic and dizygotic twins, respectively. The pairwise concordance for decline was 45% in monozygotic and 8% in dizygotic twin pairs, suggesting a possible role for genetic factors in the decline in Digit Symbol performance in this sample. A comparison of baseline biologic and behavioral characteristics within monozygotic twin pairs discordant for decline in Digit Symbol performance revealed that decliners had higher initial systolic blood pressures, lower serum cholesterol levels, and lower heart rates than nondecliners.