BACKGROUND: It was our aim to study the prevalence and possible prognostic and predictive significance of the expression of P-glycoprotein, a transmembrane transport protein related to classical multidrug resistance, in patients with advanced ovarian cancer. STUDY DESIGN: Tumor tissue from 73 previously untreated patients with FIGO stage 3 ovarian cancer was examined with immunohistochemistry for the expression of P-glycoprotein before and after chemotherapy. Response to 4 cycles of combination chemotherapy with cisplatin and epirubicin was assessed with second look laparotomy. The log rank test was used for univariate survival and the Cox proportional hazards regression model for multivariate survival analysis. RESULTS: P-glycoprotein expression was detected in 47% of untreated cases, and correlated with unfavourable prognostic factors such as advanced age, presence of ascites and larger residual disease deposits after primary surgery. P-glycoprotein negative cases responded significantly better to chemotherapy (P < .001). In the multivariate survival analysis P-glycoprotein expression was an independent predictor of both overall (P = .045) and progression free (P = .006) survival. When P-glycoprotein expression and residual disease status were considered together, the patients could be divided in three clearly distinct prognostic groups (P = .0009). CONCLUSION: P-glycoprotein expression is a predictor of response and survival in a uniformly treated and followed cohort of advanced ovarian cancer patients.