The measurement of the transmural gastric potential difference (PD) is a suitable method to quantify irritations of the human gastric mucosa caused by drugs. Purpose of this investigation was to check the gastric tolerance of Bronchoretard, a new developed "divided-dose" drug formulation of theophylline as retarded pellets in capsules in comparison to pure theophylline solution. After having checked the suitability of the procedure in respect of the obtained results, a study on 7 healthy male volunteers was considered to be justifiable, as the development of retarded theophylline preparations, which cause lower irritations in the stomach by slower release of pure theophylline, has a high therapeutic value. With the gastric PD model, developed at our institute following variables were calculated: the area under the baseline (AUB), the "Reizindex" (RI), the mean instability time (MIT) of the membrane and the maximum potential difference (Pdmax). The volunteers wee admitted to the ward of our institute 36 h before the first application. On 2 different days 350 mg theophylline, dissolved in 50 ml physiological saline as well as 1 capsule Bronchoretard containing 350 mg theophylline, were administered Cross over according to a randomisation plan and the deviation of the PD was measured as a function of time. The study led to the following results: after administration of Bronchoretard the AUB is statistically significant smaller than after administration of theophylline solution (P less than 0.05). After administration of Bronchoretard the RI is statistically significant smaller than after administration of theophylline solution (p less than 0.05). After administration of Bronchoretard the mean instability time is statistically significant smaller than after administration of theophylline solution (p less than 0.05). After administration of Bronchoretard Pdmax is smaller in trend than theophylline solution (p greater than 0.05). The oral administration of Bronchoretard leads to considerably lower irritation than the instillation of the same dose of theophylline in solution.