Rats suffer an early transient performance decrement immediately after a sufficiently large dose of ionizing radiation. However, it has been shown that males experience a more severe incapacitation than females. This sex difference has been attributed to the low estrogen levels in the male. In support of this notion, supplemental estrogens in castrated male rats have produced less-severe performance decrements post-irradiation. Antihistamines have also previously been shown to alleviate radiation's effect on behavior. The present study revealed that antihistamines are only effective in altering the behavioral incapacitation of sexually intact male subjects. This contrasts with previous work which indicates that estrogens can only benefit gonadectomized rats. These findings suggest that different mechanisms may underly antihistamine and estrogen radiation protection.