The possible site of expression of the sex difference in susceptibility to infection with Strongyloides ratti was studied in C57BL/6 mice. The intensity of infection, measured by daily larval output in faeces or by intestinal worm burden, was significantly higher in males than in females. This sex difference was already expressed during the migration of larvae from the site of subcutaneous inoculation to the cranial cavity or lung as early as 24 h after infection. Conversely, there was no significant difference in the larval output in faeces or in the worm burden of male or female recipients after implantation of adult worms using a stomach tube. When the susceptibility to infection with S. ratti of gonadectomized animals was examined, the daily larval output in faeces of orchidectomized males was significantly reduced to the level of intact females, while ovariectomy had no effect, suggesting that androgen is one of the important regulatory factors for the expression of sex difference. In fact, testosterone treatment of orchidectomized males or normal females could increase their susceptibility to or above the level of intact males. These results strongly suggest that sex difference in the susceptibility to infection with S. ratti in C57BL/6 mice is mediated by 'natural defence mechanisms' which are under the regulation of testosterone.