Eletriptan 40 mg and 80 mg have shown greater efficacy in acute migraine than oral sumatriptan 100 mg and naratriptan 2.5 mg. This study continues the systematic series of active comparator trials in the eletriptan clinical development programme. In a multicentre double-blind, double-dummy, parallel-groups trial, 1587 outpatients with migraine by IHS criteria were randomised in a 3: 3 : 3: 1 ratio to eletriptan 80 mg, eletriptan 40 mg, zolmitriptan 2.5 mg or placebo. Of these, 1312 treated a single migraine attack and recorded baseline and outcome data to be included in the intention-to-treat population. The primary analysis was between eletriptan 80 mg and zolmitriptan. For the primary efficacy end-point of 2-h headache response, rates were 74% on eletriptan 80 mg, 64% on eletriptan 40 mg, 60% on zolmitriptan (P < 0.0001 vs. eletriptan 80 mg) and 22% on placebo (P < 0.0001 vs. all active treatments). Eletriptan 80 mg was superior to zolmitriptan on all secondary end-points at 1, 2 and 24 h, in most cases with statistical significance. Eletriptan 40 mg had similar efficacy to zolmitriptan 2.5 mg in earlier end-points, and significantly (P < 0.05) lower recurrence rate and need for rescue medication over 24 h. All treatments were well tolerated; 30-42% of patients on active treatments and 40% on placebo reported all-causality adverse events that were mostly mild and transient. On patients' global ratings of treatment, both eletriptan doses scored significantly better than zolmitriptan.