OBJECTIVES: Finasteride has been shown to prolong the time off-treatment in men with prostate cancer during intermittent androgen suppression therapy, but it is not clear whether this results from an increase in prostate-specific antigen (PSA) doubling time or a delay in PSA responsiveness to regained testicular function. In the following study, we distinguish between these two possibilities and consider how the effectiveness of finasteride might be altered if androgens are synthesized within the malignant cell rather than the testis. SUBJECTS AND METHODS: Six patients were followed on intermittent androgen suppression for intervals ranging from 7 to 10 years. The effects of finasteride on the length of the off-treatment period in at least one cycle in each patient were measured with monthly determinations of serum PSA and testosterone and calculation of PSA doubling time using linear regression analysis. RESULTS: Administration of finasteride was associated with a reduction in the rate of increase of serum PSA in the off-treatment period of any given cycle within a sequence of 5. In a total of 15 cycles, finasteride extended PSA doubling time from a mean of 7.7 weeks (n = 11, range 2.3-29.8 weeks) to a mean of 45.1 weeks (n = 6, range 13.8-99.7 weeks). One patient was characterized by an apparent pseudo-resistance to finasteride in the 2nd cycle of treatment and another patient by complete resistance to finasteride in the 4th cycle. CONCLUSIONS: Finasteride can be introduced into any cycle of intermittent androgen suppression with the expectation of an extension of PSA doubling time.