We have examined whether keratinocyte growth factor (KGF) and its receptor are expressed in normal, fetal, and prostate cancer cells since KGF may play a role in the growth of adenocarcinomas. In situ hybridization studies with digoxigenin-labeled oligonucleotides (anti-sense and sense controls) were employed to examine KGF and KGF receptor mRNA expression in prostate cancer. We found that the KGF and KGF receptor genes were faintly expressed in the stromal and epithelial cells, respectively, in both fetal (n = 6) and normal adult prostate (n = 6) tissues examined. In 10 benign prostatic hyperplasias (BPH), and in low- and high-grade prostatic carcinoma (32 total), both the KGF gene and the receptor mRNA were expressed in the glandular epithelial cells. KGF was also expressed by the stromal cells in BPH and low-grade carcinoma. Computer assisted system analysis indicated that the intensity of epithelial labeling by both probes was increased in high Gleason score carcinomas ( > 8) and in metastatic nodules. We interpret the data to mean that the paracrine loop in normal prostate may be replaced by an autocrine loop in BPH and adenocarcinomas.