The effects of dihydroergocriptine (DHECP), a dihydrogenated ergot alkaloid with dopaminergic agonistic and alpha-adrenergic antagonistic properties, were studied in 22 women with PRL-secreting microprolactinomas and compared with those recorded in 36 previously studied patients treated with bromocriptine (BRC). After acute administration of 5 mg DHECP, orally, serum PRL decreased by 61 +/- 18% (+/- SD); only 1 patient was unresponsive. The nadir was reached at 300 min. Long term treatment with increasing DHECP doses caused a progressive PRL fall from 125 +/- 142 (+/- SD) to 81 +/- 159 micrograms/L after 1 week of a 3 mg twice daily regimen, to 64 +/- 88 micrograms/L after 1 week of 5 mg twice daily, 46 +/- 57 micrograms/L after 1 week of 10 mg twice daily, and 28 +/- 34 to 33 +/- 45 micrograms/L throughout 9 months of treatment with 10 mg DHECP 3 times daily. Seventy-seven percent of patients had normal serum PRL levels during chronic treatment. All women, including those with supranormal serum PRL levels, resumed regular menses, and 16 had ovulatory cycles; 1 woman became pregnant. Galactorrhea disappeared in all. During treatment the PRL response to TRH, initially absent in all patients, became positive in 10. In 7 patients, after DHECP treatment for 9 months, high definition computed tomographic scan no longer showed the focal lesions initially seen. After drug withdrawal, serum PRL increased again in all except 1 patient. Two patients had regular menses for 6 months, and 3 still had no adenoma imaged by high definition computed tomography. In BRC-treated patients the serum PRL changes and clinical results were very similar to those in the DHECP-treated patients, except for the persistence of normal serum PRL levels in 4 patients after drug withdrawal. On the other hand, side-effects were negligible during DHECP treatment, but remarkable during BRC. Systolic and diastolic blood pressures decreased by only 5.4 and 3.0 mm Hg, respectively, after acute 5 mg DHECP administration, but decreased by 12.8 and 14 mm Hg after acute 2.5 mg BRC administration. Orthostatic hypotension and peripheral vasomotor phenomena occurred in the long term DHECP treated patients except one, but they occurred in 9 and 3 of those treated with BRC, respectively. Gastric discomfort or mild nausea occurred in 12 DHECP-treated patients, while mild or severe nausea or vomiting were observed in 18, 11, and 2 of those taking BRC, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)