It has been suggested that a heparin-binding growth factor, midkine (MK), plays an important role in carcinogenesis because of its frequent overexpression in various malignant tumours. To clarify whether or not MK contributes to the early stage of carcinogenesis, we examined the status of MK mRNA in 20 adenomas with moderate-and severe-grade dysplasia, 28 carcinomas and 28 corresponding normal tissues, by means of Northern blotting. The MK expression level was significantly more elevated in adenomas than in normal tissues (P< 0.001, unpaired Student's t-test). A difference was also observed between carcinomas and the corresponding normal tissues (P< 0.04, paired Student's t-test). Moreover, MK immunostaining was positive in the adenomas with moderate-and severe-grade dysplasia and in the carcinomas, but not in mild-grade dysplasia or in normal tissues. These findings were in line with those on Western blotting. In three patients with both adenomas with moderate-or severe-grade dysplasia and carcinomas, elevated MK expression was observed in the neoplasticlesions. This is the first report of the association of elevated MK expression with the early stage of carcinogenesis in humans.