The proposed research is designed to determine the multi-stage progression and nature of renal carcinogenesis. Additional objectives are: Delineation of the relationship betweeen presumptive premalignant and malignant, N-(4'-fluoro-4-biphenyl)acetamide (FBPA)-induced renal cortical lesions and evaluation of the biological nature and behavior of presumptive premalignant renal cortical lesions by histochemistry, light microscopy and x-ray microanalysis. In pahse I male, Fisher 344 rats will be fed a diet containing FBPA (0.04% w/w) for different lengths of time from 8 to 65 weeks. Group A will receive continuous feeding of FBPA as a positive control. Group B will be fed a control diet. Group C will be fed the FBPA diet for varying times then placed on the control diet to assess the reversibility of induced lesions. Group D will be fed FBPA for 8 or 16 weeks then be fed a potential promoter, NTA or injected with TCDD to assess promotion of early lesions. Presumptive premalignant and malignant lesions throughout these studies will be characterized by histochemistry, light microscopy and x-ray microprobe techniques. In phase II rats will be injected with 1 dose of FBPA followed by chronic treatment with TCDD or NTA in experiments designed to assess the multi-stage nature of FBPA-initiated renal carcinogenesis. Gross and microscopic lesions in animals from all protocols will be quantified by accepted techniques and statistical analysis will be performed between appropriate groups.