1. We tested the hypothesis that patients with an acute attack of migraine headache and low serum levels (< 0.54 mmol/l) of ionized magnesium are more likely to respond to an intravenous infusion of magnesium sulphate (MgSO4) than patients with higher serum ionized magnesium levels. 2. Serum ionized magnesium levels were drawn immediately before infusion of 1 g of MgSO4 in 40 consecutive patients with an acute migraine headache. 3. Pain reduction of 50% or more as measured on a headache intensity verbal scale of 1 to 10, occurred within 15 min of infusion in 35 patients. In 21 patients, at least this degree of improvement or complete relief persisted for 24h or more. Pain relief lasted at least 24h in 18 of 21 patients (86%) with serum ionized magnesium levels below 0.54 mmol/l, and in 3 of 19 patients (16%) with ionized magnesium levels at or above 0.54 mmol/l (P < 0.001). Mean ionized magnesium levels in patients with relief lasting for at least 24h were significantly lower than in patients with no relief or brief relief (P < 0.01). 4. Measurement of serum ionized magnesium levels may be useful in identifying patients with migraine headaches who may respond to an intravenous infusion of MgSO4.