The level of transforming growth factor beta1 (TGFbeta1) and transforming growth factor betaII receptor (TGFbetaRII) was determined immunohistochemically in normal tissues and tissues with different severities of lesions (basal cell hyperplasia, BCH; dysplasia, DYS; carcinoma in situ, CIS; and squamous cell carcinoma, SCC) from surgically resected human esophagi and esophageal biopsies of symptom-free subjects. The samples were from an area with high esophageal cancer incidence in northern China (Linzhou, formerly Linxian, and nearby county Huixian in Henan Province). Peroxidase immunostain (ABC) and conventional hematoxylin and eosin stain were used. The tissue sections were incubated with antibodies of TGFbeta1 and TGFbetaRII overnight. The immunoreactivity was observed in cytoplasm of the esophageal specimen. From normal to BCH to DYS to CIS and to SCC, the positive immunostaining rates for TGFbeta1 increased significantly (P < 0.05). A linear correlation between the positive immunostaining rates of TGFbeta1 and the different lesions was observed (P < 0.05). From well- to moderately- and poorly differentiated SCC, the positive immunostaining rates for TGFbeta1 decreased gradually, but the difference was not significant (P > 0.05). In contrast, with the lesions progressing from normal to BCH to DYS to CIS and to SCC, the positive immunostaining rates for TGFbetaRII decreased significantly (P < 0.05). From well- to moderately- and poorly differentiated SCC, the positive immunostaining rates for TGFbetaRII decreased significantly (P < 0.05). There was a linear correlation between the positive rates of TGFbetaRII and different lesions and SCC differentiation (P < 0.05). The present results indicated that the alterations of TGFbeta1 and TGFbetaRII is a frequent event in esophageal multistage carcinogenesis, the absent or lower expression of TGFbetaRII may lead to the loss of cell proliferation control by TGFbeta1 and the overexpression of TGFbeta1 may be a negative feedback response caused by the lower expression of TGFbetaRII protein.