To enrich a small population of malignant cells contaminating human bone marrow or peripheral blood, a method of immunomagnetic depletion of the normal nucleated cells was developed. In a model using neuroectodermal cell lines, contaminations between 0.1% and 1.4% of tumor cells could be increased by a factor of 7.5 (median; range, 3.8 to 18.0; n = 10). Because incubation with antibodies is restricted to the magnetic beads in this method, the cell population after removal of the beads has not been incubated with antibodies. The risk of unspecific staining of the tumor cells during the enrichment procedure is minimal. This simple method is therefore well suited to the study of the characteristics of a minimal residual disease population.