Neurotensin receptor expression was studied in 19 human colon cancer cell lines and normal human colon by i) binding experiments using [125I-Tyr3]-neurotensin; ii) RT-PCR analysis. The following data were obtained: 1) A single class of receptor (Kd ranging from 0.23 to 1.21 nM) was found in 9 out of 19 cell lines but not in normal colonic epithelium; 2) The Bmax was in the range between 1000 and 85 fmoles/mg protein with SW48 > WiDR > Cl 19A > HCT116 > SW480 > SW620 > Cl 16E > Cl 27H > HT-29. No specific binding was measurable in Caco-2, FRI, CBS, EB, HCT-8, 320HRS, 320DM and LS174T cell lines; 3) A single RT-PCR product was observed in HT-29, SW48, WIDR, Cl 19A, SW480, Cl 16E, Cl 27H, SW620 and HCT116, but not in other cell lines or in normal human colon. It is concluded that the expression of neurotensin receptors in human colon cancer cells is regulated at the mRNA level and occurs upon malignancy in > 40% of colon cancer cell lines.