Synaptic efficacy at the laryngeal neuromuscular synapse differs markedly in adult male and female Xenopus laevis. Here, we examined the relation between circulating estrogen and synapse strength in developing and adult female frogs. Circulating estrogen levels in males and females during juvenile and adult stages were measured using radioimmunoassays. Synaptic strength was determined by quantal analysis in isolated female larynges. In males, estrogen levels are low (<40 pg/mL) throughout development. In females, estrogen levels are similar to those in males until 9 months after metamorphosis is complete and then increase throughout development. Female laryngeal synapses have low quantal contents until 24 months; quantal content increases significantly between 24 and 26 months, and high quantal contents are maintained thereafter. Measures of reproductive maturation, ovary, and oviduct weights, are strongly and positively correlated with estrogen level in 16- to 26-month females, while oocyte maturation is age dependent. Estrogen level and quantal content are not well correlated in these females. Ovariectomy at 24 months prevents the expected increase in quantal content and ovariectomy at 28 months results in a decrease in quantal content. Thus, the sex difference in efficacy of the laryngeal synapse develops under the influence of the ovary and requires the ovary for maintenance of strong synapses in adulthood. While the influence of the ovary is most likely due to estrogen secretion, the pattern of estrogen secretion required for maturation of the synapse in females is not known.