The possible interaction of a steady-state cetirizine treatment, a nonsedating H1 antihistamine, on the disposition of a single I.V. infusion of theophylline was studied in six healthy male volunteers. As a corollary, it was checked whether this single theophylline administration modified the steady-state condition of cetirizine. A three-period, two-treatment, crossover design was used, each period being separated by a washout of 1 week. Each period consisted of the oral administration of 10 mg cetirizine or of a matching placebo every 12 h for 31/2 days, the last intake being followed, 1 hour later, by a single 1-h I.V. infusion of 240 mg theophylline or of placebo. The sequence of treatments (A = cetirizine + theophylline placebo, B = cetirizine placebo + theophylline, C = cetirizine + theophylline) was allotted by a double Latin-square randomization. The repeated administration of cetirizine induced a 3% decrease of the urinary elimination of unchanged theophylline; the total body clearance of theophylline was marginally (+5%) and not significantly modified. Theophylline slightly lengthened the elimination half-life of cetirizine (from 8.3 to 9.9 h), without modification of its apparent total body clearance; the half-life of cetirizine remaining in the normal range. These subtle modifications are not clinically relevant and it may, thus, be considered that cetirizine exerts no pertinent interaction on theophylline disposition.