Serotonin (5-hydroxytryptamine, 5-HT) is assumed to play a role in the pathophysiology of different psychiatric disorders including alcoholism. Since platelets and central serotonergic synaptosomes share similar pharmacodynamics of 5-HT, this study determined platelet 5-HT concentration in 148 male and 42 female drug-free subjects with alcohol dependency, according to the DSM-IV criteria, and in sex-and age-matched controls. Male and female alcoholics had significantly lower platelet 5-HT concentration than 110 male and 123 female healthy controls. Sex differences, i.e. higher platelet 5-HT concentration in men than in women, were found both in healthy and alcoholic subjects. Platelet 5-HT concentration differed significantly in male and female alcoholic subjects with or without different psychiatric comorbidities. Platelet 5-HT concentration was higher in male alcoholics with comorbid posttraumatic stress disorder (PTSD) than in male alcoholics with comorbid anxious-depressive disorder, or depression, or male alcoholics without any psychiatric comorbidities. Comorbid depression in female alcoholics slightly elevated platelet 5-HT levels but these values were still reduced compared to values in healthy women. Smoking status did not affect platelet 5-HT concentration either in healthy or in alcoholic subjects. The data from our study show sex differences, and reduced platelet 5-HT values, regardless of the nicotine dependence, in the large groups of male and female alcoholic subjects. Among male alcoholics the presence of comorbid PTSD partly normalized the decreased platelet 5-HT values. The results of the present study support the hypothesis that alterations in 5-HT system might be related to alcoholism.