The use of intercavernous sinus phlebography for the diagnosis and neurosurgical treatment of pituitary adenomas has enabled the collection of selective venous samplings of the inferior petrosal sinuses (IPSs), where prolactin (PRL) levels can be measured before the hormone becomes excessively diluted in the systemic circulation. In the present study, plasma PRL levels were studied in the right and/or left IPS and, simultaneously, in the peripheral circulation of: (1) normoprolactinemic patients affected with various pituitary disorders which required phlebographic procedures; (2) hyperprolactinemic patients with negative radiological and computed tomographic (CT) signs of pituitary adenomas and (3) adenomatous hyperprolactinemic patients. In the 17 normoprolactinemic patients, the plasma PRL concentration in the IPSs was significantly higher (3.5 times; p less than 0.01) than in the peripheral circulation. In the 11 hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas, the central gradient for PRL was significantly higher (2.8 times; p less than 0.05) than in the peripheral circulation. No significant difference was detected between PRL concentrations in the left and right IPSs. In the 11 adenomatous hyperprolactinemic patients, there was a significant (p less than 0.01) central gradient for PRL 3.8 times higher than in the peripheral circulation on the ipsilateral side of the tumor. Furthermore, the plasma PRL concentration in the ipsilateral IPS was significantly higher (3.4 times; p less than 0.05) than that in the contralateral sinus. In conclusion, the present study shows that a clear-cut concentration gradient exists between plasma PRL levels in the IPSs and in the peripheral circulation of normoprolactinemic and hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)