Drug resistance in cancer is a major obstacle to successful chemotherapy. Cancer cells exposed to antitumour drugs may be directly induced to express a subset of genes that could confer resistance, thus allowing a population of cells to survive and form the relapsed resistant tumour. Alternatively, some cancer cells may be expressing an array of genes that could confer intrinsic resistance, and exposure to cytotoxic drugs select for the survival of these cells that form the relapsed tumour. To assess whether there are differences in the mechanism of drug resistance by induction or selection, we used complementary DNA (cDNA) microarray to monitor mRNA expression in breast cancer cells that were either transiently treated with or selected for resistance to doxorubicin. Expression profiles of the human breast carcinoma MCF-7 cells transiently treated with doxorubicin were compared with those obtained from a MCF-7 cell line selected for resistance to doxorubicin. Transient treatment with doxorubicin altered the expression of a diverse group of genes in a time-dependent manner. We found a subset of transiently induced genes constitutively overexpressed in cells selected for resistance to doxorubicin, suggesting that cancer cells activate a distinct set of genes in acquiring drug resistance by either induction or selection. Our studies demonstrate the feasibility of obtaining molecular profiles of drug resistance in cancer cells by cDNA microarray, which might yield insights into the mechanisms of resistance during chemotherapy, and suggest alternative methods of treatment.