Thirty human renal cell carcinomas, subpassaged into NMRI-nu/nu mice, were analyzed during long term serial transplantation (range, 10-50 passages) with regard to their histological differentiation, mitotic activity, and DNA content. A quantitative methodology was applied to determine the mitotic rate. The DNA content was measured by flow cytometry. Only five tumors (four primaries and one metastasis) changed their mitotic rate significantly (P less than 0.01). In each case this change was paralleled by a simultaneous alteration of the DNA content. Histological pattern and nuclear grade remained stable in all but one tumor where the change in histological pattern occurred simultaneously with changes in DNA index and mitotic rate. These results indicate that the majority of renal cell carcinomas remain stable during long term serial transplantation, at least with regard to the parameters examined. This is a basic prerequisite for making the grafting of renal cell carcinomas into nude mice a reliable in vivo model for drug sensitivity testing. However, since a few of the transplanted tumors showed instability, continuous monitoring of phenotypic and genotypic tumor features is necessary during long term xenotransplantation.