Interaction between the hypothalamo-pituitary-adrenal axis and the serotonergic system is thought to be disrupted in chronic fatigue syndrome (CFS) patients. We examined a serotonin transporter (5-HTT) gene promoter polymorphism, which affects the transcriptional efficiency of 5-HTT, in 78 CFS patients using PCR amplification of the blood genomic DNA. A significant increase of longer (L and XL) alleic variants was found in the CFS patients compared to the controls both by the genotype-wise and the allele-wise analyses (both p < 0.05, by chi(2) test and Fisher's exact test). Attenuated concentration of extracellular serotonin due to longer variants may cause higher susceptibility to CFS. (C) 2003 Elsevier Inc. All rights reserved.