Antiandrogens are combined with medical or surgical castration to achieve total androgen blockade in metastatic prostate cancer. Discontinuation of antiandrogens at disease progression has been associated with prostate-specific antigen (PSA) decrease, symptom improvement, and occasionally objective tumor regression. Two cases of metastatic prostate cancer demonstrating decrease in PSA of 92% and 56% on discontinuation of nilutamide therapy are reported. Improvement in urinary symptoms, bone pain and, in one, disappearance of para-aortic lymphadenopathy paralleled the PSA decrease. The duration of the withdrawal response of 6 months was comparable to those reported with discontinuation of flutamide.