The effects of a new PRL inhibitor, CV 205-502 (CV), on human macroprolactinomas were studied in nine patients according to a prospective protocol. Five patients had undergone surgery leaving tumor remnants and persistent hyperprolactinemia. The four others were de novo patients, two of whom had received short term treatment with Parlodel. Plasma PRL levels ranged from 235-6050 micrograms/L before treatment. The doses of CV used in this trial ranged from 0.075-0.600 mg. Plasma PRL normalized in eight of the nine patients during treatment with CV. The time to normalize varied from 2 weeks to 9 months, and the doses from 0.075-0.450 mg. A tumor volume reduction of more than 50% was obtained in all four patients who had not been operated on before CV treatment. Only one of the five patients with postoperative tumor remnants had no reduction in tumor size. The drug was generally well tolerated, and no patient interrupted the treatment. Slight and short-lasting gastrointestinal symptoms were noted in several patients, and a single episode of fainting occurred in one patient when the drug was not taken at bedtime as instructed. A noticeable and persistent weight loss with anorexia was noted in two patients. Since CV 205-502, administered in a single daily dose, has tolerable side-effects and is effective in reducing PRL secretion and tumor size, it can be considered to be a useful treatment for macroprolactinomas.