Cathepsin D (Cath D) levels were assayed in a prospective series of 72 patients with primary ovarian carcinoma, by using an immunoradiometric assay. Cath D levels ranged from 2.00 to 45.60 pmol/mg protein with a median value of 15.80 pmol/mg protein. Cath D levels were higher in metastatic deposits than in primary tumors (median 24.12, range 9.33-98.33 pmol/mg protein versus median 12.76, range 2.00-45.20 pmol/mg protein; P = 0.04). The cut-off levels of the lower, median and upper quartiles of the distribution of Cath D were identified to distinguish patients with low, intermediate, and high Cath D content. Cases with low Cath D content showed a lower percentage of complete response to chemotherapy than cases with intermediate and high Cath D content (22% versus 65% and 47%, respectively) (P = 0.003). Moreover cases with high Cath D content showed a worse prognosis with respect to patients with intermediate Cath D levels (P = 0.09). Interestingly, cases with low Cath D content had a shorter progression-free survival with respect to cases with intermediate Cath D content (P = 0.04). Cath D status retained an independent prognostic value when assessed in the multivariate analysis.