Tryptophan (Trp) metabolism and disposition and excitatory and other amino acid concentrations were determined in alcohol-dependent subjects in relation to the alcohol-withdrawal syndrome (AWS). Parameters were examined in 12 alcohol-dependent male subjects, undergoing elective upper digestive tract tumour resection, and 12 age-, gender-, and medication-matched controls on three occasions: pre-operatively, post-operatively, and immediately before (i.e. within 24 h of) the appearance of the AWS. No significant differences were observed between controls and alcoholic subjects on the first or second of these occasions. On the third occasion, within 24 h of the appearance of the AWS, alcoholics showed a dramatic elevation (117%) in free serum Trp concentration and a consequent increase (111%) in the ratio of [free Trp]/[competing amino acids], which is an accurate predictor of Trp entry into the brain. Increases were also observed on this third occasion in concentrations of total Trp (49%), cortisol (123%), and norharman (137%). Concentrations of glutamate, glycine, aspartate, serine, and taurine did not differ significantly within or between the control and alcohol-dependent groups of subjects on any of the three occasions. The possible significance of the Trp and related metabolic changes in relation to the behavioural features of the AWS is discussed.