Fetal raphe cells were transplanted into the anterior corpus callosum (CC) of serotonin (5-HT)-denervated hydrocephalic rats. The levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were measured in the anterior and posterior parts of the CC at 1-2, 5-6, and 7-8 weeks posttransplantation. The 5-HT and 5-HIAA levels in the anterior part were restored to their maximum within 5-6 weeks posttransplantation in both hydrocephalic and nonhydrocephalic rats. In contrast, the 5-HT and 5-HIAA levels in the posterior part continued to increase for the period beyond 5-6 weeks posttransplantation. The longer time course of the restoration in the posterior part may reflect the time for fiber growth from the site of transplantation to remote brain areas. Hydrocephalic rats showed slightly higher levels of 5-HT (154.4%) and 5-HIAA (159.5%) in the anterior part, and markedly higher levels of 5-HT (254.8%) and 5-HIAA (388.7%) in the posterior part at 5-6 weeks posttransplantation, compared with nonhydrocephalic rats. These results imply favorable effects of interstitial edema associated with hydrocephalus on the survival of transplanted raphe cells and fiber outgrowth.