We have investigated the effect of TRH on the release of GH in 20 acromegalic patients (14 females and 6 males) before and after selective removal of a pituitary tumour via transsphenoidal route. The follow-up period was 8 years. Pre-operatively the paradoxical response was present in 15 patients (75%). Mean GH values in TRH responders were significantly lower than in non-responders. According to the size and expansion diffusion of the adenoma, the patients were divided into 3 classes. The percentage of paradoxical response in patients in class III was significantly lower than in the other two classes. Postoperatively, mean GH values in pre-operative TRH responders were significantly lower than in non-responders; among 15 responders, 13 (86%) had postoperative GH levels under 5 micrograms/l; among 5 non-responders only 2 (40%) had GH values under 5 micrograms/l. Postoperatively 8 patients still had GH responsiveness to TRH: 6 with GH levels persistently (follow-up 8 years) under 5 micrograms/l and 2 with elevated GH values. The other 7 patients, who were responders pre-operatively and non-responders postoperatively, persistently exhibited low GH levels, except one subject who showed an increase in GH levels with reappearance of the paradoxical response, two years after surgery. These results suggest: 1. the paradoxical response may be expressed only when the hypothalamus-pituitary interactions are intact; 2. the disappearance of the paradoxical response cannot surely suggest a remission, and 3. the presence of a pre-operative paradoxical response is a good prognostic feature.