Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85 -27.2 mg ml À1 paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT -PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P ¼ 0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P ¼ 0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P ¼ 0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols. Taxanes like paclitaxel play an important role in the adjuvant treatment of breast cancer (Henderson et al, 2003). The efficacy of paclitaxel containing treatment can be further improved by dose dense protocols in which the chemotherapy is administered every 2 weeks with G-CSF support. Arguably, sequential protocols in which paclitaxel is administered not only dose dense, but also dose intensified, might prove to be even more efficient. Despite the well-documented antitumour efficacy of paclitaxel, many tumours exhibit intrinsic resistance to paclitaxel. These patients will obviously not profit from addition of paclitaxel to an anthracycline-based adjuvant chemotherapy. Identifying these patients could not only spare them an ineffective treatment, but gives the opportunity to establish a more efficient protocol for this particular subgroup of paclitaxel-resistant patients. In the adjuvant setting, Henderson et al (2003) have shown that especially patients whose tumours were oestrogen receptor (ER) negative derived most of the benefit from adding paclitaxel to an anthracyclin-based regimen. However, it is not entirely clear whether in this setting the prognostic impact of the hormone receptor status and the effect of adjuvant treatment with tamoxifen might thus offset a potential predictive effect of the hormone receptor status for paclitaxel chemosensitivity.