To investigate the effect of plasma free fatty acids (FFA) elevations on growth hormone (GH) secretion in humans, paired physical exercise (ph.e.) tests were performed in 9 untrained healthy volunteers of both sexes. Ph.e. tests were accomplished on a bicycle ergometer under a moderate work load (450 kpm/min .times. 40 min). On 1 of 2 test days, subjects were given 60 g of a soy bean oil emulsion (Intralipid) 3 h before, followed by two 50 mg heparin bolus injection, administered 10 min before and 15 min after the start of the exercise. Ph.e. in the control group induced a clear-cut elevation of GH levels which peaks at 40 min. Intralipid plus heparin induced FFA elevation, completely block GH secretion elicited by exercise (P < 0.05 at 20 and 40 min). There also seems to be a threshold level of FFA (3 meq/l) above which GH suppression was complete. Below this level GH blockade was rather inconsistent. FFA elevation blocked all the GH stimuli tested so far, and this data support a role of plasma FFA in GH regulation.