Root nodulation is regulated by a variety of mechanisms. Ecto-apyrase is an enzyme proposed to control the concentration of extracellular nucleotides. Transgenic expression of the soybean GS52 ecto-apyrase was shown to stimulate nodulation. However, mutation of the enzyme to disrupt enzymatic activity prevented this effect. Therefore, the data suggest that the enzymatic activity of the ecto-apyrase is critical for nodulation enhancement, suggesting a direct effect on extracellular nucleotide hydrolysis. In this article, we propose a hypothetical mechanism for plant ecto-apyrase function during nodulation.