Twenty-three patients with low natural killer syndrome (LNKS), 7 males and 16 females, are reported here. These LNKS patients had an age range from 14 to 77 years, with a median of 36.5 years. LNKS is a newly proposed category of immune disorders, being characteristically diagnosed by lowered NK cell activity against K562 target cells as a definite laboratory abnormality, in association with general clinical symptoms of remittent fever and uncomfortable fatigue, persisting without explanation for more than 6 months. Other immune parameters, such as the DNA synthesis of peripheral blood mononuclear cells (PBMCs) in either the presence or absence of mitogens, the T4+/T8+ ratio and the number of Leu-11+ PBMCs, were usually within the normal range. Also, routine laboratory tests did not detect any abnormal findings. The LNKS patients responded well to the administration of an immunopotentiator called 'lentinan', a glucan extracted from the Japanese mushroom Lentinus edodes, despite no responses to conventional fever treatments such as the administration of antipyretics or antibiotics. All LNKS patients observed were universally free of antibodies in their sera to human T-lymphotropic retroviruses I and III, and lymphadenopathy was infrequent, indicating that the LNKS is a syndrome independent of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Antibodies to other known viruses tested such as Epstein-Barr or measles virus, or cytomegalovirus were also negative or not significantly elevated in the sera before the initiation of lentinan administration. If a virus is the cause of LNKS, it may be a new, unknown virus or an unknown substrain of known viruses. None of the LNKS patients has died of this syndrome.