Neuropeptides have recently been implicated in regulation of normal and neoplastic cell growth. Substance K is a neurotransmittor candidate that has been identified as a mitogen for smooth muscle cells and fibroblasts. However, the ability to respond to stimulation with substance K declines rapidly in cells serum-starved for more than 24 h and in parallel with a decrease in the intracellular level of myc-gene transcripts. Contrarily, myc-transformed cells, that inspite of a decrease demonstrated a high level of myc mRNA after 48 h in serum-free medium, maintained their ability to initiate DNA synthesis when stimulated with substance K. The results suggest that the intracellular signal of substance K-induced DNA synthesis interacts with the myc protein.