We investigated the pattern of GH secretion in response to repetitive TRH administration in patients with active acromegaly and in normal subjects. Nine acromegalic patients and 10 normal subjects received three doses of 200 micrograms of TRH iv at 90-min intervals. There was a marked serum GH rise in acromegalic patients after each TRH dose (net incremental area under the curve [nAUC]: first dose = 4448 +/- 1635 micrograms.min.l-1; second dose = 3647 +/- 1645 micrograms.min.l-1; third dose = 4497 +/- 2416 micrograms.min.l-1; NS), though individual GH responses were very variable. In normal subjects TRH did not elicit GH secretion even after repeated stimulation. Each TRH administration stimulated PRL release in acromegalic patients, though the nAUC of PRL was significantly higher after the first (1260 +/- 249 micrograms.min.l-1) than after the second and the third TRH administration (478 +/- 195 and 615 +/- 117 micrograms.min.l-1, respectively; P less than 0.01). In normal subjects too, PRL secretion was lower after repeated stimulation (first dose = 1712 +/- 438 micrograms.min.l-1; second dose = 797 +/- 177 micrograms.min.l-1; third dose = 903 +/- 229 micrograms.min.l-1 P less than 0.01), though different kinetics of PRL secretion were evident, when compared with acromegalic patients. TSH secretion, assessed in only 4 patients, was stimulated after each TRH dose, though a minimal but significant reduction of nAUC of TSH after repeated TRH challenge occurred. Both T3 and T4 increased steadily in the 4 patients. The same pattern of TSH, T3, and T4 secretion occurred in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)