The effects of bombesin/gastrin-releasing peptide ( BN GRP) on c-fos and c-jun gene expression were investigated using small cell lung cancer (SCLC) cells. BN (10nM) increased c-fos mRNA fivefold using NCI-H345 or NCI-H510 cells. The increase was concentration dependent with 1 nM BN half-maximally increasing c-fos mRNA. Also, the increase in c-fos mRNA caused by BN was time dependent, being maximal after 1 h and returning to basal values after 4 h. GRP and GRP(14-27) but not GRP(1-16) increased c-fos mRNA. BW2258U89 (1 μM), a GRP receptor antagonist, had no effect on basal c-fos but inhibited the increase in c-fos mRNA caused by 10 nM BN. Also, BN transiently increased c-jun mRNA twofold and the increase caused by BN was blocked by BW2258U89. These data suggest that GRP receptors may regulate nuclear oncogene gene expression in SCLC cells. © 1995.