Small-cell lung cancer (SCLC) synthesises a wide range of neuropeptides and their corresponding receptors. Together, these can form autocrine growth loops. Non-small-cell lung cancer (NSCLC) does not generally share this neuroendocrine phenotype. In this study, we tested the hypothesis that multiple neuropeptides and their receptors are co-expressed in SCLC, constituting potential autocrine loops. Expression of mRNA for arginine vasopressin, gastrin, cholecystokinin, gastrin-releasing peptide, endothelin and neurotensin, together with their cognate receptors, was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) in a panel of human lung cancer cell lines. We have assessed those neuropeptides and neuropeptide receptors that could be used as potential early markers to detect lung cancer cells both as micrometastases in blood and within dysplasia in bronchial biopsies. We establish that although no cell line expressed all neuropeptides, co-expression of neuropeptides and their receptors is common in SCLC but not in NSCLC. We conclude that mRNA for the neuropeptides gastrin-releasing peptide and arginine vasopressin and the cholecystokinin receptor B were most SCLC-specific and RT-PCR for these markers could be used to distinguish between SCLC and NSCLC.