Seven new multidrug resistant variants of six established cell lines were developed with the drug adriamycin, HEP-2A, HEP-2B, DLKP-A, OAW42-A, SKMES1-A, SKLU1-A and DLRP-A. All the cell lines, except for DLRP-A were found to cross resistant to a range of drugs. There is a consistent rank order correlation between resistance to the selecting drug and cross resistance to other drugs. The detailed cross resistant profile varies markedly among cell lines selected with the same drug. Heterogenity in the level of drug resistance was a feature of all the MDR variants tested. The MDR variants were generally found to have altered biophysical properties, with sensitivity to standard freezing and standard subculture procedures noted. Additionally, the MDR variants were found to be more resistant to sonication, indicating possible altered lipid composition of the cell membranes. The P-170 mechanism of resistance was investigated by Western Blotting, Immunofluorescence and antisense transfection, and was found to be involved in resistance in CHrC5, DLKP-A, HEP-2A, HEP-2B, SKMES1-A and OAW42-A. There are however indications of other mechanisms of resistance, (e.g. cross resistance to 5-Flurouracil and cis-platin). Additionally incomplete reversal of resistance by Antisense oligomer transfection is suggestive of alternative mechanisms of resistance to P-170 present in a number of the cell lines. SKLU1-A was negative in all the P-170 studies so alternative mechanisms of resistance must be causative reason of MDR in this cell line. Cytogenetic manifestation of MDR in the form of DMs was evident in DLKP-A, HEP-2A and HEP-2B, Drug resistant cell lines were generated by transfection with a complete murine cDNA for mdrl. The drug resistance pattern observed were significantly different from those of the variants obtained by adaptation from the corresponding parental cell line. It was possible to circumvent adriamycin resistance with clinically relevant doses of a number of compounds, verapamil, quinine, quinidine, nifedipine, chloroquinine, caffeine, generic and standard aspirin.