The effects of bombesin, vasoactive intestinal polypeptide (VIP), and a somatostatin analog (RC-160) on the in vitro invasion of reconstituted basement membrane (Matrigel) by two human prostatic carcinoma cell lines were examined. Aggressively growing PC-3 cells were found to be invasive in this assay in contrast to the relatively indolent LNCaP cells. Bombesin increased penetration of basement membrane by both cell lines. Although VIP had no effect on invasion by PC-3 cells, it enhanced invasion by LNCaP cells in a dose-dependent manner. In agreement with these results, VIP stimulated adenylate cyclase activity only in LNCaP cells. In contrast to bombesin and VIP, RC-160 did not alter invasion by either cell line. Our results suggest that certain neuroendocrine peptides can increase the invasive potential of prostatic carcinoma cells and may thereby contribute to the rapid progression and aggressive clinical course of prostate tumors containing neuroendocrine elements.