The hyperglycemic response to multiple low-dose SZ injections was measured in castrated and non-castrated male and female mice with or without testosterone treatment. On the 10th day of the experiment, control males had plasma glucose concentrations that were significantly higher than those of control females. Castration of males decreased the hyperglycemic response, while testosterone treatment restored it. The glucose concentrations in castrated females were significantly greater than control females, but not different from castrated males. Testosterone administration to castrated or non-castrated females increased the hyperglycemic response to that seen in control males and in testosterone-treated castrated males. Thus, castration negates the sex difference in the hyperglycemic response to the multiple low-dose SZ injections. Testosterone enhances the hyperglycemic response in castrated or non-castrated females, and in castrated males.