Two experiments were conducted to determine the effect of free fatty acids (FFA) and glucose treatment on growth hormone (GH) and luteinizing hormone secretion in the pig. In Experiment (Exp) 1, 15 prepuberal gilts received an intravenous infusion of FFA (n = 5; 3 ml of 10% Liposyn II/kg), glucose (n = 5; 1 g/kg), or saline (n = 5; 3 ml of 0.9%/kg). Jugular blood samples were collected every 15 min for 2 hr before and 3 hr after intravenous infusion of saline, FFA, and glucose. Synthetic [Ala15]-h growth hormone-releasing factor-(1-29)NH2 (1-mu-g/kg) and gonadotropin-releasing hormone (0.2-mu-g/kg) were administered 30 min after infusion (Time 0 = infusion). In Exp 2, eight prepuberal gilts received either FFA (n = 4) or saline (n = 4) as described in Exp 1, except that treatments were given every hour over a 10-hr period. Blood samples were collected every 15 min from 1 hr before to 10 hr after the start of FFA or saline infusion. In Exp 1, the peak GH response to growth hormone-releasing factor was delayed by 45 min (P < 0.01) by glucose treatment and suppressed (P < 0.01) by FFA treatment. The luteinizing hormone response to gonadotroph-releasing hormone was suppressed (P < 0.03) by glucose and enhanced (P < 0.03) by FFA. In Exp 2, the number of GH pulses was increased (P < 0.05) by FFA infusion and GH concentrations were positively correlated (r = 0.58, P < 0.0003) with FFA concentrations, while luteinizing hormone pulse amplitude was greater (P < 0.01) in FFA gilts than in saline gilts. These results indicate that FFA are more effective modulators of GH secretion than acute hyperglycemia, while metabolic status can alter pituitary responsiveness to gonadotropin-releasing hormone.