Differentiating HiB5 cells, a rat hippocampal cell line, expressed neuregulins and showed constitutive activation of a neuregulin receptor, ErbB2, suggesting development of a neuregulin autocrine loop. RT-PCR analyses indicated that HiB5 cells produced SMDF and NDF, but not GGF, during the differentiation. None of neuregulin isoforms were detected in proliferating HiB5 cells. The neuregulins in HiBS cells, at least in part, are the $eta$-isoforms of which the most of neuronal neuregulin isoforms are. The expression of SMDF and NDF was enhanced by PDGF and bFGF that promote cell survival and differentiation, suggesting a close relationship between the synthesis of neuregulins and the differentiation process. HiB5 cells have ErbB2 and ErbB4, but not ErbB3 receptors. Constitutive tyrosine phosphorylation of ErbB2 was detected in HiB5 cells that had not been exposed to exogenous GGF.