High affinity 3H-paroxetine binding was studied in human frontal cortex and hippocampus obtained from normal controls and alcoholics. On the basis of Scatchard analyses, a significant decrease in the maximal number of binding sites (Bmax) was found in the hippocampus of alcoholics (n = 8) as compared with that of controls (n = 10) (mean +/- SD = 63 +/- 35 vs. 114 +/- 70 fmoles/mg protein). There was no significant difference in the dissociation constants (Kd) between the two groups. The presumed effect of chronic alcohol abuse on 3H-paroxetine binding may be region-specific since no significant difference in either Bmax or Kd for 3H-paroxetine binding was found in the frontal cortex between normal controls and alcoholics. No significant correlation of 3H-paroxetine binding with age or postmortem interval was observed. The decrease in 3H-paroxetine binding in the hippocampus of alcoholics is probably indicative of reduced density of serotonergic nerve terminals either as a preexisting condition or as a result of neuronal damage caused by ethanol or the sequelae of alcoholism, such as nutritional deficiencies.