This open-label, crossover study had two objectives: to compare the steady-state pharmacokinetics of high-dose telmisartan with and without coadministered high-dose hydrochlorothiazide and to compare the steady-state pharmacokinetics of hydrochlorothiazide with and without coadministered telmisartan. A total of 13 healthy males and females of nonchildbearing potential received the following oral, once-daily medications, each for 7 days: telmisartan 160 mg, hydrochlorothiazide 25 mg, and telmisartan 160 mg plus hydrochlorothiazide 25 mg. Between medication periods, there was a 14-day washout. Blood was collected at intervals over 48 and 84 hours, respectively, at the end of the 7-day dosing period for the determination of plasma telmisartan and hydrochlorothiazide concentrations by high-performance liquid chromatography. Predose blood samples were also collected on days 1, 6, and 7. Tolerability of single-agent and combination medication was monitored. For hydrochlorothiazide and telmisartan, given alone or in combination, there were no appreciable differences in trough plasma concentrations between days 6, 7, and 8; thus, at day 7, both agents had achieved steady state. Mean values of the primary end points (Cmax and AUC0-24) and secondary end points (Cmin and t1/2) for both telmisartan and hyrochlorothiazide were unaffected when administered simultaneously. Moreover, concurrent telmisartan had no effect on urinary excretion of hydrochlorothiazide. Transient lightheadedness, associated with postural hypotension, was the most common adverse event. The absence of any significant effects on the pharmacokinetics of either hydrochlorothiazide or telmisartan shows that no dose adjustment is required if the two agents are given concurrently for the management of hypertension.