Nuclear PCNA immunoreactivity is found in the proliferating compartment of normal and tumor cells. The purpose of the present study was to examine immunohistochemical staining of PCNA in renal cell carcinoma and its relationship to tumor grading, flow cytometric DNA analysis and prognosis. The resected kidneys from 81 patients with renal cell carcinoma were used. Anti-PCNA monoclonal antibody was applied to paraffin sections to identify proliferating cells by the SAB technique. The proportion of PCNA-positive cells to negative cells was determined by counting the tumor cells stained by PCNA at 400x magnification and expressed as percentage of positive cells. In parallel with the PCNA immunostaining DNA flow cytometry was performed, using the cell suspension prepared from paraffin sections and stained with propidium iodide. 79 tumors were evaluable for PCNA immunohistochemistry and 54 tumors for DNA flow cytometry. Immunohistochemically, there was no significant difference in percentage of PCNA-positive cells between tumor grades G 1 and G 2 (1.4 +/- 1.3% in G 1 and 1.6 +/- 1.4% in G 2), while G 3 tumors contained high percentage of PCNA positive cells, the mean value being 7.6 +/- 5.3%. The percentage of PCNA-positive tumor cells was found to be correlated with histological grading of tumor and also with the S+G2+M phase fraction and the S phase fraction measured by flow cytometry (p < 0.01). The mean percentage of PCNA-positive tumor cells was higher in aneuploid tumors than in diploid tumors. There was no significant relationship between the percentage of PCNA positive cells and tumor staging. Sixty-one cases were available for survival analysis.(ABSTRACT TRUNCATED AT 250 WORDS)