Multiple myeloma is a disease which is generally considered responsive to chemotherapy; however, essentially all patients who respond to drug treatment will relapse and die of drug-resistant disease. This disease is therefore considered a paradigm for studying the development of acquired drug resistance in the clinic. Natural product agents are frequently used in the treatment of myeloma, especially vincristine and doxorubicin. Studies using human myeloma cell lines have shown that the MDR1 gene product, P-glycoprotein (Pgp), is responsible for conferring drug resistance to natural products and glucocorticoids. We have developed assays to measure the expression of MDR1/Pgp in human myeloma specimens. These assays include immunocytochemistry, flow cytometry, and RT/PCR. Human myeloma cell lines, 8226/Dox, that are resistant to natural product agents and overexpress MDR1/Pgp are important for standardizing results and offer a means of comparing inter- and intra-patient results. Assays which measure both the presence and function of Pgp are necessary to determine the role of Pgp in clinical drug resistance in patients with myeloma.