Fifteen human placentas were obtained at term. Placental fragments were incubated in a bicarbonate-buffered Earle's solution. Additions of glutamate (1 mM) or glutamine (1 or 2 mM) were made. All incubations showed a net utilization of glucose. There was a striking variability among placentas in the net glucose utilization rate (1.27 mumoles/g/hr-11.44 mumoles/g/hr, coefficient of variation = 62%). The intraplacental coefficient of variation in glucose utilization was only 14%. All placental incubations showed a net production of both lactate (mean = 7.5 mumoles/g placental wet weight/hr) and ammonia (mean = 3.5 mumoles/g placental wet weight/hr). There was no correlation between lactate of ammonia production and glucose utilization. The addition of sodium glutamate (1 mumole/ml) produced no change in glucose utilization or ammonia production. The addition of glutamine (1 and 2 mumoles/ml) produced a significant increase in ammonia production over that found in the controls, but no change in glucose utilization. Incubation with 2 mumoles glutamine/ml demonstrated an increase in lactate production. All incubations showed a striking increase in ammonia concentration after 45 min of incubation. Individual placentas may differ markedly in their ability to utilize glucose in an in vitro system. Ammonia production may be a normal metabolic endproduct in a tissue lacking an active urea cycle or a byproduct of the purine nucleotide cycle.