Mouse embryonic stem (ES) cells were transplanted into the cochlea of adult guinea pigs in order to explore their survival, differentiation, and possible integration with the host tissue. With the purpose of investigating the possible effect of manipulating the local embryonic microenvironment, ES cells were transplanted into the cochlea with or without an embryonic neuronal cograft consisting of dorsal root ganglion (DRG) tissue. To detect the survival and differentiation of ES cells, cells expressing green fluorescent protein (GFP) were used in combination with immunohistochemical detection of a neuronal marker, neural class III beta-tubulin (TUJ1 antibody). At 4 weeks following transplantation implanted ES cells were found close both to the sensory epithelium, and the spiral ganglion neurons (SGNs) with their peripheral dendritic processes projecting to the organ of Corti. There was a significant difference in the number of surviving TUJ1 (+) ES cells between the DRG cograft group and the non-cograft group (P < 0.01, ANOVA). Neurite-like projections were also identified between TUJ1-positive ES cells and the peripheral dendritic processes from SGNs. The results suggest that an embryonic neuronal microenvironment may be one of the key factors in the survival and differentiation of ES cells in the adult auditory system.