The gamma-aminobutyric acid (GABA) neurotransmitter system has been implicated in the pathogenesis of manic depression. Tests of this hypothesis can now be carried out due to the recent characterization of simple sequence repeat polymorphisms for the GABAA receptor alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, beta 1, beta 3 and gamma 2 subunit genes. Using both parametric and non-parametric methods, we tested for linkage between manic depression and these polymorphisms in six multi-generational pedigrees. No evidence of linkage was found.