Complex and conflicting relationships between epidermal growth factor (EGF), estrogens (E), androgens (A), and related receptors (EGF-R, E-R, A-R) have been reported in different biological situations associated with cell proliferation. There is also evidence that EGF and sex hormone receptors may be involved in normal and neoplastic growth of the gastrointestinal mucosa. In this study, we investigated the behavior of EGF receptors and sex hormone and related receptors, during N-methyl-N'-nitro-N-nitrosoguanidine (NG)-induced gastric carcinogenesis in Sprague-Dawley male rats. Four groups of 15 rats each (10 NG-treated and five controls) were sacrificed after 1, 20, 30, and 40 weeks of treatment. Gastric tissue from each rat was processed for receptor status (number and affinity) and proliferative activity. A significant and progressive decrease of A-R and EGF-R was observed starting from the 20th week, while no change of E-R occurred throughout the experiment. Cell proliferation in the gastric mucosa of NG-treated rats increased after 30 weeks of treatment. These data indicate that NG treatment is able to modify the receptor status of gastric mucosa in rats.