Handedness data collected during the Hawaii Family Study of Cognition were congruent with similar data from major published studies. Mixed-model segregation analysis did not detect a significant major gene or polygenes contributing to handedness and partitioned the total phenotypic variation into 10–20% genetic and 80–90% environmental components. No relationship between handedness and cognitive ability was detected, but significant relationships between birth stress and offspring handedness were found. There was a significant decline in the percentage of left-handed individuals grouped by advancing age. A hypothesis of handedness is proposed in which left-handedness results from a combination of genotype, birth experience, and maternal example.