To determine the efficacy of a diuretic agent, hydrochlorothiazide, as second-line therapy after failed alpha-blocker therapy for men with nocturia. The study inclusion criteria were a < 25% reduction in nocturia using the International Prostate Symptom Score question 7, a < 25% reduction in nocturia using the frequency-volume chart, and/or nocturia > or = 2/night (according to the frequency-volume chart) after 4 weeks of terazosin therapy. A total of 72 patients were entered into the study and treated with 25 mg of hydrochlorothiazide and 4 mg of terazosin once daily for 4 weeks. Of the 72 eligible men, 53 completed the study. No serious side effects occurred among the treated patients. Using the International Prostate Symptom Score, a reduction of > or = 50%, 25%-49%, 0%-24% and an increase in nocturia was observed in 7, 7, 31, and 8 patients, respectively. Using the frequency-volume chart, 17 patients reported reduced nocturia by more than one half, 5 reported a reduction of 25%-49%, and 31 reported no response to treatment or an increase in nocturia. At baseline, all except for 1 patient had nocturnal polyuria (nocturnal polyuria index > 33%), and, after the combination therapy, the nocturnal polyuria had resolved in 6 (11.5%) of the 52 patients with nocturnal polyuria at baseline. Hydrochlorothiazide combined with terazosin was safe and effective in reducing nocturnal frequency for some men after failed terazosin therapy. Our findings suggest that the use of a diuretic agent, such as hydrochlorothiazide, might be a reasonable second-line treatment option for these patients, especially for those with nocturnal polyuria.