Autoimmune dysfunction of certain vasoactive neuropeptides (e.g., vasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide) may be implicated in a range of disorders associated with fatigue-like states (chronic fatigue syndrome, Gulf War syndrome) and even sudden infant death syndrome (SIDS). The important roles of these vasoactive neuropeptides make them a vulnerable target for autoimmune dysfunction. They are known to be associated with heat shock proteins for intracellular functioning with which they may form immunostimulating complexes. Cytosine guanine dinucleotide (CpG) fragments are potently immunogenic DNA fragments which serve as friend or foe recognition systems between bacterial (hypomethylated) and mammalian (methylated) DNA and are being assessed for suitability for use in human vaccines as adjuvants. Interactions between CpG fragments, heat shock proteins and vasoactive neuropeptides may be associated with fatigue-related autoimmune conditions.