Plasma gamma-aminobutyric acid (GABA) levels are decreased in some patients with depression, mania and alcoholism. Medications which increase plasma GABA improve symptoms of mood disorders and can decrease aggression. We examined the relationship between plasma GABA and aggressiveness on the Buss-Durkee Hostility Inventory in 77 psychiatrically healthy adults. In subjects selected for having a first-degree relative with primary unipolar depressive disorder (FH+, n=33), plasma GABA was negatively correlated with aggressiveness (beta=-0.338, P=0.036), as was age (beta=-0.483, P=0.005). A relationship between plasma GABA levels and aggressiveness was not observed in subjects with no such family history (FH-, n=44). Moreover, FH+ subjects had significantly lower plasma GABA concentrations than FH- subjects. These data suggest that low GABA levels may correlate with some aspects of aggressiveness and may be genetically regulated.