Thyroid hormones (THs), primarily 3,3′,5-triiode-L-thyronine (T3), have been clearly established as natural inducers of apoptosis during metamorphosis of anuran embryos. We decided to use this phenomenon to test the hypothesis that, prior to genomic activation, T3 has acute actions in the neuromuscular junction (NMJ) of the tail of amphibian embryos. We detected a dramatic increase in the production of miniature end-plate currents (MEPCs) 2–5 min after continuous application of T3 (250 nM) using focal recordings under voltage clamp. Furthermore, this increase in the spontaneous release of neurotransmitter, evaluated by the MEPC frequency, was maintained for several hours. Reverse-T3, the “inhibitory” form of THs, prevented this increase in MEPC frequency, suggesting that this is probably a highly specific action of T3. In addition, the elevation in MEPC frequency induced by T3 was unchanged in the presence or absence of extracellular calcium. The T3-mediated increase in MEPC frequency was blocked by niflumic acid, a nonsteroidal antinflammatory fenamate used to prevent the apoptotic volume decrease observed in many systems. The present study demonstrated that T3 induces a remarkable nongenomic action in the NMJ of the tadpole tail at pre- and promatamorphic stages. © 2002 Wiley-Liss, Inc.