The GABA system is closely linked to the biochemical pathophysiology of alcohol intoxication, dependence, and withdrawal. Previous research has shown plasma GABA, which reflects brain GABA activity, to be low in a subset of patients with alcohol dependence 2-4 weeks after cessation of drinking. We now report on a study of GABA, with simultaneous measures in cerebrospinal fluid (CSF) and plasma, in 14 male alcoholdependent patients during acute alcohol withdrawal (day 1) and again after 21 days of inpatient treatment (Day 21). On admission, plasma GABA levels correlated with indices of liver function. When corrected for differences in liver function, plasma levels of GABA on day 1 were significantly higher than on day 21 (p < 0.001). CSF levels of GABA were also higher during withdrawal than after 3 weeks of abstinence, although this difference was only a trend (p < 0.1). The change in plasma GABA levels correlated significantly with the change in CSF GABA levels (r = 0.69, p = 0.006); however, plasma GABA and CSF GABA levels did not show a significant correlation at either time point studied. Although the present study did not incorporate controls, levels of plasma GABA were significantly lower than the established normal range for healthy controls of 100-150 pmol/ml. These findings replicate our previous work showing plasma GABA levels to correlate with liver function in recently detoxifled alcoholics, and to decrease after abstinence. Also, this work suggests that changes in CSF GABA may be reflected in plasma GABA, adding to the validity of the peripheral marker. Whether low GABA in alcoholics reflects an induced deficit or a vulnerability awaits further research.