A 74-year-old man underwent irradiation therapy (RT) to the prostate bed because of prostate-specific antigen (PSA) failure after retropubic radical prostatectomy (RRP). Six months after the RT, a solitary bone metastasis developed in the third thoracic vertebra, and hormonal therapy (HT) was initiated. Three years later, following the loss of response to all hormonal agents, including oral estrogen and glucocorticoid therapy, paraplegia developed, due to a spinal metastasis. RT and high-dose glucocorticoid therapy were given for the spinal metastasis. Diethylstilbestrol diphosphate (DES-DP) was given continuously during this treatment, except for a 1-month period when the patient had pneumonia. After the RT and high-dose glucocorticoid therapy, his serum PSA decreased, from 308 to 36.99 ng/ml. In accordance with the 1-month discontinuation, and then resumption of DES-DP, the serum PSA levels went up and down. So we suspected that the tumor had recovered sensitivity to DES-DP with the high-dose glucocorticoid therapy. With a further decrease of serum PSA to 2.12 ng/ml, he has been alive for more than 3 years to date since the diagnosis of hormone-refractory prostate cancer (HRPCA). To our knowledge, there have been no reports showing such a marked recovery of hormone-sensitivity in HRPCA. No optimal therapy has yet been established for HRPCA; therefore, high-dose glucocorticoid therapy in combination with DES-DP warrants further study.