A role for gamma-aminobutyric acid (GABA) in the pathophysiology of schizophrenia was first suggested by Eugene Roberts in 1972. Since then considerable work has been accomplished in both the clinical and basic sciences regarding GABA and schizophrenia. Although it was originally thought that GABA might be useful in treating schizophrenia because of its inhibition of dopaminergic activity, recent data have shown that in certain models GABA has the opposite effect on dopaminergic functions. Regardless of the relationships of GABA to dopamine, neither biochemical nor pharmacological studies have been able to demonstrate a clear and reproducible GABA disturbance in schizophrenia. A number of problems contribute to the difficulty in studying GABA in schizophrenia, including the lack of specific and nontoxic GABA agonists as well as the complexity of the GABA system in brain. Interest in GABA research in schizophrenia appears to have waned, but several areas nevertheless appear promising for clinical investigation.