One of the major obstacles to successful autologous bone marrow transplantation is tumor contamination of the marrow. We attempted to separate tumor cells from the marrow of patients with small cell lung cancer by layering bone marrow on a discontinuous albumin gradient and then assessing hematopoietic potential (CFUc) and clonogenic tumor cells (TCFUc) by standard techniques. In the six of seven patients whose bone marrow grew tumor colonies, 75 to 80% of CFUc could be found in Fraction 3 of the gradient; while 80 to 90% of TCFUc could be found in light-density Fraction 1 + 2. Furthermore, we observed tumor colony growth in Fraction 1 + 2 in some patients whose unfractionated bone marrow failed to grow tumor colonies. In separate experiments, we layered five cell lines established in patients with small cell lung cancer on the gradient and found that cells from four of the five lines also migrated to Fraction 1 + 2, and TCFUc from these lines were observed in Fractions 1 + 2 in three of four lines tested. We conclude that gradient fractionation may be one way of removing clonogenic tumor cells from the bone marrow of small cell lung cancer patients prior to autologous transplantation.