Hypogonadal mice with a genetic deficiency of gonadotropin-releasing hormone (GnRH) have low levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and gonadal steroids. In this study we found differences from normal mice in many aspects of thymic development. Thymus weights and cellularity were higher in hypogonadal than in normal male mice but lower in hypogonadal than in normal females. Although all normal mice had higher proportions of mature, single staining thymocytes (CD8+ or CD4+) than seen in hypogonadal mice, there was a sex difference in the basis for this shift. Significantly more double-staining (CD8+, CD4+) thymocytes were seen in hypogonadal males than in normal males while both groups had similar single-staining populations. However, in females, both single-staining CD8+ and CD4+ thymocytes were more numerous in normal than in hypogonadal females while numbers of double-staining cells were similar in the two groups. These studies indicate that a mature thymocyte profile may be arrived at through differential effects of reproductive hormones in males and females. When brain grafts containing GnRH cells were used to correct reproductive deficits in hypogonadal mice, there were higher splenocyte counts in males with grafts, a similar trend in females, and a lower ratio of single staining CD4+ to CD8+ thymocytes in all females with grafts vs. all females without, regardless of whether or not the grafts corrected the reproductive hormone status of the recipients, indicating an effect of the graft surgery on the immune system.