Renal cell carcinoma (RCC), of which the clear cell subtype is most frequently seen, represents the most frequent malignant tumor of the kidney and shows, even after radical nephrectomy, a hardly predictable long-term outcome as well as a low responsiveness to irradiation or chemotherapeutic drugs. Since in the recent past the eminent importance of apoptosis for tumor formation and growth due to its influence on proliferation became evident, the present study examinated the expression of apoptosis- and proliferation-related proteins in clear cell RCC, their interrelations and their possible prognostic impact. In specimens of 23 formaline-fixed, paraffin-embedded clear cell RCC, the expression patterns of Bcl-2, Ki-67, p53 and VHL where detected by immunostaining, and the number of apoptotic cells was estimated using the TUNEL method. The examined parameters were evaluated regarding their associations with each other and with pT tumor stage and nuclear grading as well as their influence on progression-free survival. 43.5% of the examined RCC showed apoptotic activity, and a higher frequency of apoptosis was closely related with an higher nuclear grading. The counts of Ki-67 positive cells were low and did not show any association with clinicopathological parameters; but there was a significantly positive correlation with p53 and VHL protein expression. All RCC demonstrated a high Bcl 2 positivity, however, the extend of Bcl-2 expression was not significantly correlated with one of the other immunohistochemical or clinicopathological parameters. The p53 expression of the 23 RCC was relatively high: 60.1% of the NZK showed > 1% p53-positive cells; 43.5% demonstrated a positive staining in > 5 % of the cells. The p53 and VHL expression where closely related. Almost 40% of the RCC showed a complete loss of VHL-expression. There was a tendancy towards a lower progression-free survival among patients whose tumors showed 20 % VHL-positive cells. Nuclear grading and pT stage were significantly correlated. These results suggest a possible meaning of apoptotic counts and, perhaps, VHL expression patterns as prognosticators in clear cell RCC. In addition, p53 alterations in clear cell RCC seem to be more common than frequently assumed. Considering the positive correlation between p53 and VHL expression, alterations of these genes could be alternative mechanisms of carcinogenesis in RCC. The high overall Bcl-2 expression implies a functional meaning of this protein for clear cell RCC and offers a possible pharmacological target for its treatment.