Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma who had developed progressive disease following therapy with one 5-FU-based regimen. Fourteen patients were treated with flutamide, 250 mg orally three times per day. Therapy was generally well tolerated. No patients achieved objective tumor response. No patient had improvement in tumor-related symptoms as measured by improvement in pain intensity, analgesic requirement, performance status, or nutritional status. Median survival was 4.7 months. We conclude that flutamide is ineffective second line therapy for patients with advanced pancreatic adenocarcinoma.