Changes in growth hormone (gh) release in response to L-dopa, TRH, arginine and LH-RH were studied in 15 patients with acromegaly to investigate the mechanism of so-called 'paradoxical decrease' of GH secretion often observed in acromegalics after the administration of L-dopa. Among 15 patients, 11 showed GH increase with TRH, 8 with arginine, and 4 with LH-RH. On the other hand, six out of these 15 patients showed a distinct paradoxical GH decrease after L-dopa administration. Two cases showed an increase in GH on L-dopa as seen in normal subjects. The responses of GH release, either an increase or a decrease, was proved fairly constant when several patients had been examined repeatedly. Changes of GH induced by L-dopa were compared wwith those by TRH, arginine, and LH-RH. There were no correlation between the changes by L-dopa and those by TRH, arginine, and LH-RH when compared simply. But a significant negative correlation (r=-0.861) was found between percent changes by L-dopa and logarithm of increase ratio (peak value of GH after the stimulation/basal value) induced by TRH. More close correlation (r=-0.881) was obtained when the percent changes by L-dopa was (formula: see text). This result would imply that paradoxical GH decrease by L-dopa in acromegalic patients is more remarkable when their GH secretion is more responsive to TRH and less responsive to arginine. When this correlation is considered in connection with the reported effects of L-dopa on GH and thyroid stimulating hormne (TSH) in man, the following hypothesis might be proposed: L-dopa has two opposing actions on the hypothalamo-pituitary system; 1) inhibition of TRH release or suppression of GH release from TRH sensitive GH producing cells, and 2) arginine-like facilitation of GH release presumably via stimulation of GH-RF. The paradoxical GH decrease in acromegalics on L-dopa is explained by the dominance of the former action.