We examined the expression of the mdr1 gene in 90 human tumor cell lines of which 79 were derived from leukemia or lymphoma samples. Using Northern blot analysis and the mdr1.1 probe, only three cell lines, KB-V1 (a positive control), EM-2, A-704, displayed mdr1 mRNA expression. Immunocytochemical APAAP staining of these three and 15 other cell lines with the anti-p170 glycoprotein monoclonal antibody JSB-1 was negative in all but the KB-V1 cells. In contrast to the results seen in freshly explanted neoplastic cells, the mdr1 gene does not seem to be functionally expressed in the majority of unmanipulated and unselected, continuous human tumor cell lines.