The angiotensin (ANG II) AT2 receptor mediates antiproliferative effects and induces neurite outgrowth in PC12W cells. To further investigate the molecular events following AT2 receptor stimulation in these cells, we determined the expression pattern of the middle-sized neurofilament subunit (NF-M) using Western and Northern blot analysis and reverse-transcription polymerase chain reaction. On both, the protein and the mRNA level, ANG II via AT2 receptors not only counteracted nerve growth factor (NGF)-mediated NF-M up-regulation but also reduced NF-M levels in the absence of NGF by maximally 72%. The ANG II-induced effects were completely abolished by pretreatment with the AT2 receptor antagonist, PD123177. In view of previous findings of decreased NF levels in regenerating neurons and in neuronal cultures undergoing apoptosis, our observation suggests a new role of AT2 receptors in either of these processes.