We have developed a new method to determine free as well as sulfoconjugated salsolinol (SAL), separated into both enantiomers, and free and sulfoconjugated dopamine in human blood plasma. Among the group of nonalcoholics (R)-SAL (mean +/- SEM: 0.24 +/- 0.07 ng/ml) was found in all blood samples and (S)-SAL in 1 out of 20 (0.08 ng/ml). Ethanol loading induced a rise of both enantiomers as well as of dopamine whereby (S)-SAL was detected in the plasma of 13 subjects only [(R)-SAL: 0.79 +/- 0.24 ng/ml; (S)-SAL: 0.49 +/- 0.15 ng/ml; DA: 8.84 +/- 0.75 ng/ml]. The later finding favors the notion of an enzymatic formation of (S)-SAL. In alcoholics, (R)-SAL and (S)-SAL were elevated at the day of admission for detoxification [(R)-SAL: 0.65 +/- 0.82 ng/ml; (S)-SAL: 0.35 +/- 0.05 ng/ml] and normalized after several months, suggesting intoxication marker characteristics [month 6: (R)-SAL: 0.24 +/- 0.14 ng/ml; (S)-SAL: 0.20 +/- 0.05 ng/ml]. Patients with alcoholic parents had lowered (R)-SAL and (S)-SAL levels compared with family history negative alcoholics, suggesting genetic association of disturbance of the SAL biosynthesis and alcoholism. Among the personality traits, suicidality was linked with low (R)-SAL and (S)-SAL concentrations in contrast to novelty seeking, impulsivity, and harm avoidance scores. The scores on the self-rating anxiety scale correlated positive with (R)-SAL. These findings suggest trait marker characteristics of salsolinol.