To examine the duration of serum testosterone and prostate-specific antigen suppression after each dose of a 4-month depot leuprolide acetate for 18 months and to assess the potential for using serum testosterone as a guide for redosing the luteinizing hormone-releasing hormone analogs instead of using fixed dosing intervals. Luteinizing hormone-releasing hormone analogs are well established for the treatment of prostate cancer (PCa). However, many open questions remain regarding the optimal dosing. Thirteen patients with PCa were enrolled in a longitudinal study. Serum testosterone levels were obtained at baseline and then monthly beginning 4 months after the first injection and every 2 months after the subsequent injections, for a total of 18 months. The median number of days from injection to the first serum testosterone level > or = 50 ng/dL was estimated using the Kaplan-Meier product-limit method. The median duration of effect was 159, 189, and 163 days for the first, second, and third treatment cycle, respectively. The prostate-specific antigen values from entry to completion decreased in all subjects. The total number of injections was reduced in all but one subject who completed the 18-month trial. One patient developed hormone-refractory PCa. Serum testosterone measurement might be a useful method for redosing luteinizing hormone-releasing hormone analogs. Using testosterone levels to determine the time of reinjection has a significant economic impact. Monitoring serum testosterone not only helps to identify patients who fail to achieve testosterone suppression but also provides close monitoring for the potential development of hormone-refractory PCa.