The 35Cl(alpha, n)38K nuclear reaction was developed for the routine cyclotron production of repeated multimillicurie batches of 38K for dynamic studies of regional tissue perfusion with positron emission tomography. The objective is to make this isotope available as an alternative to the use of [13N]NH3 and 82Rb for the investigation of flow in experimental and clinical use. A sodium chloride powder target mounted on a water-cooled nickel backing is bombarded with 26 MeV helium-4 ions at a maximum beam current of 25 microA. The target is remotely disconnected from the bombardment port, transported to a hot cell and entirely processed by a computer-controlled system within a total time of less than 4 min. The final pyrogen-free isotonic and sterile solution of 38K has a radionuclidic purity of more than 99.99%. A typical yield of 19 +/- 2 mCi of 38K is obtained at the end of a 30 min bombardment at 10 microA. The production rate at saturation can therefore be estimated to 2.05 +/- 0.2 mCi/microA.