ISO-1, a Δ²-isoxazoline, displays anti-diabetogenic activity as an MIF antagonist. In our method to prepare this class of compounds, we noted an interesting tandem reaction. β,γ-Unsaturated ketones were treated with a strong base (NaOH) and hydroxylamine hydrochloride (NH₂OH.HCl) in warm aqueous ethanol to yield 3,5-disubstituted Δ²-isoxazolines in a single step. The mechanism and scope of this reaction will be discussed.