A prospective, randomized study of the potential protective effects of corticosteroids administered as pretreatment against contrast material (CM) reactions is reported. Patients (n = 6,763) from multiple institutions received either a single dose of steroids (32 mg of oral methylprednisolone, approximately 2 hours before CM challenge), a double dose (32 mg approximately 12 hours and 2 hours before CM challenge), or placebo. All contrast injections were with ionic media and were given intravenously. The two-dose (but not the one-dose) corticosteroid regimen provided significant protection. The effect on reaction incidences of a number of historical variables is also tabulated.