To study the effect of hypoxia on humoral immunity function of rat and Ochotona curzoniae (pika), the specific antibody production to novel antigen IgG and immunoresponse to sheep red blood cell (hemolysin forming) were measured. The results show that hypoxia at altitude of 5 km and 7 km for 10 d resulted respectively in 10.3% (P < 0.05) and 21.9% (P < 0.05) decrement in hemolysin formation in rats, as compared with the control group kept at 2.3 km. When the rats were secondarily immunized and kept at the same hypoxia for 10 d, the reduction in hemolysin formation was 4.2% (P < 0.05) and 4.6% (P < 0.05) for the two respective altitudes. These changes, however, were not found in pikas. When rats were immunized two days before hypoxia, 5 km hypoxia for 5 d and 8 d failed to suppress hemolysin formation. Intracerebroventricular (i.c.v.) injection of CRF (1.0 microgram/rat), decreased hemolysin formation and production of IgG by 8.6% (P < 0.05) and 14.0% (P < 0.05) respectively, but intraperitoneal (i.p.) injection of CRF (1.0 microgram/rat) had no effect. On the other hand, i.c.v. injection of CRF receptor antagonist (alpha-helical CRF (9-41), 50 micrograms/rat) prior to 7 km hypoxia caused a hypoxia-induced suppression of IgG production from 24.2% to 12.1% (P < 0.05). Adrenalectomy in rats lowered hemolysin formation by 6.6% (P < 0.05). The above results demonstrate that hypoxia suppresses humoral immunity function and alters initial antigen processing probably through an increase of CRF in the central nervous system.