Recently baking soda has been promoted to control coqui frogs. While some concentrations of baking soda may be effective, the only legal and Environmental Protection Agency (EPA)-approved agents for controlling coqui frogs are citric acid and hydrated lime. Use of baking soda as a frog control agent has not been approved by the EPA; therefore it would be a violation of EPA regulations to use it for that purpose.

Citric acid is on a list of substances that are exempt from EPA regulations because it is generally recognized as safe, whereas sodium bicarbonate is not exempt. A 16% citric acid solution is recommended as a treatment against coqui frogs. In 2005, the EPA granted a 3 year permit for 3% hydrated lime solution to be used as a coqui frog control agent based upon efficacy data and an environmental assessment.

Tests conducted by USDA APHIS Wildlife Services, National Wildlife Research Center in Hilo showed that both the 16% citric acid and 3% hydrated lime solutions killed nearly 100% of coqui frogs - including males, females with eggs (gravid), and juveniles - upon direct contact with either solution. Mortality is based on contact with the solution, not the sex or reproductive state of the frog.

The female coqui frog lays eggs within hours of fertilization by the male. Female frogs are therefore not considered "pregnant". Coqui frogs are unusual among frogs in that the male guards the fertilized eggs by sitting on them until they hatch into fully formed froglets approximately two weeks later. This extraordinary amount of parental care helps to protect the eggs from predators, disease, and dehydration.

Occasionally people find frogs that remained alive in treated areas and may conclude that treatment was ineffective, but it is more likely that those survivors managed to avoid direct contact with the chemical solution. Adult coqui frogs are about the size of a quarter, and are capable of hiding in very small cracks, under vegetation, and on the undersides of leaves. If either solution is used or mixed improperly, is washed away by rain or irrigation, or if frogs do not come into direct contact with it, then effectiveness is reduced.