The diagnosis of familial Mediterranean fever has been one of exclusion. In a placebo-controlled, double-blind, cross-over study a challenge with a 10 mg dose of metaraminol infusion was followed within 48 h by a typical disease-like attack in all of 21 patients with familial Mediterranean fever but in none of 21 control subjects. The induced attacks were milder and of shorter duration than the spontaneous ones. The metaraminol-induced symptoms were similar to the natural disease attacks and could be prevented with prophylactic colchicine therapy. No significant side-effects were observed.