We have investigated a panel of human lung cancer cell lines representing the major groups of lung cancer, i.e., small-cell carcinoma (SCC) and the group of non-SCC, consisting of squamous-cell carcinoma (SQC), adenocarcinoma (ADC) and large-cell carcinoma (LCC), for their expression of certain growth factor genes. Messenger RNA from each cell line was hybridized with probes for platelet-derived growth factor (PDGF) A- and B-chains, insulin-like growth factor (IGF)-I and -II, transforming growth factor (TGF)-alpha and -beta, epidermal growth factor (EGF) as well as a probe for the EGF receptor. All non-SCC cell lines examined showed expression of the PDGF A-chain gene. The PDGF beta-chain and TGF-beta genes were expressed in all non-SCC cell lines but one, H-125 (ADC). TGF-alpha gene expression was demonstrated in the SQC cell line U-1752, in both ADC cell lines (H-23 and H-125) and in one of the 3 LCC cell lines, U-1810. IGF-II was only transcribed in the LCC cell line U-1810. The EGF-receptor was detected in all non-SCC cell lines but one, H-661 (LCC). Neither IGF-I nor EGF transcripts could be seen in any of the 10 cell lines examined. In contrast to the non-SCC cell lines, the 4 SCC lines were constantly negative for the probes employed in this study. The frequent and heterogeneous expression of growth factor transcripts in all non-SCC studied, but not SCC-cell lines, may contribute to the difference in biological behaviour observed in vivo and in vitro between the 2 major lung cancer entities.