The adult rabbit cornea synthesizes cyclic AMP in response to both serotonin and isoproterenol. The authors have examined the postnatal development of these pathways and attempted to localize the responsive cell type(s) by dissection, cell culture, and surgical denervation. Full thickness corneas of neonatal rabbits have beta-adrenergic responses similar to the adult but fail to respond to serotonin until the animals are 9-12 weeks old. When adult corneas are separated into epithelia, stromal, and endothelial layers, only the stromal layer synthesizes cyclic AMP in response to serotonin, whereas all layers respond to isoproterenol. When grown in tissue culture, keratocytes, epithelial, and endothelial cells are unresponsive to serotonin but respond to isoproterenol. Neither adrenergic nor sensory denervation abolishes the corneal adrenergic or serotonergic response pathways. These results indicate that the epithelial cells do not contain the serotonin stimulated, cyclic AMP-mediated pathway as originally postulated. The cell population that does contain this pathway is within the stroma and may be the Schwann cells.