The sudden unexplained death syndrome (SUDS) is a sudden death of unknown cause in healthy South-East Asians. In Thailand, it is common in the North-East region. We previously reported high incidences of low erythrocyte sodium and potassium-activated adenosine triphosphatase (NaK-ATPase) activity and of high erythrocyte sodium in North-East Thais and speculated that this metabolic defect might be associated with the high incidence of SUDS in that region. In this communication, we studied plasma sodium and potassium, erythrocyte sodium and potassium, activities of erythrocyte NaK-ATPase, ouabain-insensitive ATPase and total ATPase in healthy Thai blood donors from Central Thailand (group 1), healthy North-East city dwellers (group 2), relatives of SUDS victims (group 3) and survivors from SUDS-like attacks (group 4). Compared with groups 1 and 2, group 3 and 4 subjects had significantly lower plasma potassium (p < 0.0001), higher erythrocyte sodium (p < 0.0001), lower activities of erythrocyte NaK-ATPase (p < 0.0001) and of erythrocyte total ATPase (p < 0.0001). In addition, group 4 subjects had lower plasma potassium, higher erythrocyte sodium and lower activity of total ATPase than those of group 3. The findings suggest that the pathogenesis of SUDS could be related to hypokalemia and a membrane sodium/potassium pump defect.