mdr1 expression by reverse transcription and polymerase chain reaction (RT-PCR) has been compared to P-glycoprotein (Pgp) expression by immunohistochemistry (IHC) and correlated with clinical response to neoadjuvant therapy. RNA has been recovered from glass slide smears of fine-needle aspiration from 57 untreated primary breast cancers prior to neoadjuvant chemotherapy (33 cases), hormone therapy (23 cases), or both (1 case). Furthermore, mdr1 mRNA has been analyzed in 6 cases after 2 months of treatment. The neoadjuvant therapy consisted of 4 cycles of adriamycin and cyclophosphamide or tamoxifen. Of 57 tumor specimens, an interpretable result was obtained in 52 cases, indicating the feasibility of the analysis by RT-PCR with very small tumor specimens. The presence of mdr1 mRNA has been documented in 44/52 (84%) tumor samples with a spectrum of expression levels. The expression of mdr1 mRNA was compared with P-glycoprotein (Pgp) expression by IHC using JSB-1, 4E3, and C494 monoclonal antibodies in 48 of the 52 interpretable tumor samples. 12/48 (25%) expressed Pgp by IHC. All tumors expressing Pgp by IHC were also positive by RT-PCR. The results confirm the higher prevalence of mdr1 mRNA compared to the protein expression. However, mdr1 mRNA expression was found to correlate significantly with resistance to neoadjuvant hormone therapy only while Pgp expression detected by JSB-1 immunostaining only correlated with chemoresistance. The lack of convincing correlation with chemoresistance suggests that mRNA and Pgp may not be directly or solely responsible for clinical response to drugs. Further studies should focus on the post-translational modulation of P-glycoprotein and other mechanisms of drug resistance.