Growth factors in general and transforming growth factor-alpha in particular have been related to cell proliferation and cell differentiation. This study was designed to clarify the distribution pattem of TGF-alpha in chemically-induced hepatocarcinogenesis. Sprague- Dawley rats were subjected to different non-intensive or intensive carcinogenic treatments using diethylnitrosamine (DEN) as carcinogen and ethinyl estradiol (EE) as promoter. The livers were fixed in 2% paraformaldehyde, dehydrated in a series of ethanol solutions, embedded in paraffin and sectioned. In the preneoplastic lesions no TGF-alpha immunoreactive cells were identified, but in some hepatic tumours cell immunostained with TGF-alpha antibody were observed. These results suggest that the cells capable of expressing TGF-a constitutively may be involved in neoplastic development in vivo.