Experimental therapeutic models require the availability of sensitive and quantitative methods for assessing tumor burden and response to therapy; conventional approaches typically involve direct macroscopic or microscopic measurement of tumor mass. We are exploring the application of molecular biologic approaches to development of new in vivo metastatic, orthotopic and other xenograft models where more precise quantitative determination of tumor burden is critical. Utilizing probes for repetitive human DNA sequences, we have demonstrated that human tumor DNA can be detected in DNA extracted from whole mouse organs and that this signal can be utilized to characterize the time-course and tissue distribution of metastatic cells. Future work will be directed towards improving methods of dot-blot quantitation, application of the polymerase chain reaction to enhancement of sensitivity for detection of human DNA sequences and application of DNA probe technology to evaluation of therapeutic effects.