We have studied the effects of doxorubicin on the gene expression profiles of the K562 cell line and its doxorubicin-resistant variant, K562DoxR using hybridization of labeled complementary DNAs obtained from the messenger RNA population of treated and untreated cells with 1,176 cDNA probes spotted on Atlas membranes (Clontech). We added doxorubicin to cell cultures in the exponential phase of growth at a concentration corresponding to its IC50 value in each cell line (1.2 μM for K562 cells, 32 μM for K562DoxR cells). Exposure times were 2, 4, 8, 24 and 48 h. We first checked that the relative signal intensities were reproducible for the hybridization step (average of 1,176 CVs=16%) as well as for the retrotranscription and hybridization steps taken together (average of 1,176 CVs=18%). The transcriptome was strongly altered by drug treatment, the alterations generally increasing with drug exposure time. In K562 cells after 24 h of drug treatment 18 genes out of 1,176 seemed to be at least fivefold overexpressed and 38 at least fivefold underexpressed. After 48 h these figures were 97 and 228, respectively. Among the most affected genes were those encoding growth factors and their receptors, transcription factors and genes related to DNA repair and apoptosis. These preliminary results allow the identification of the functions involved in cell response to doxorubicin. The kinetic analysis of the gene expression profiles may yield insights into the sequence of the initial events leading to cell death or cell resistance after drug exposure.