The author evaluated the hypothesis that the incidence of allergic-type adverse events among atopic and asthmatic cardiac angiography patients would be lower in patients randomized to receive nonionic versus ionic lower osmolal contrast medium. Enrollment criteria included a history of food allergy, asthma, atopic dermatitis or pollinosis but not prior contrast media-induced adverse events. One hundred forty-two patients enrolled were randomized to receive either the ionic agent ioxaglate or nonionic iopamidol. Patients and investigators were masked. Sixty-eight patients received iopamidol, and 74 received ioxaglate. Group means were compared using the unpaired Student's t test. Contingency tables were analyzed using chi-square or Fisher's exact test. Allergic-type adverse events (excluding flushing, warmth, and cardiac events) were recorded in 8 of 68 patients in the iopamidol group versus 19 of 74 in the ioxaglate group. Ioxaglate was more likely to be associated with a reaction than iopamidol (P < 0.05, chi-square test). Iopamidol was more likely to be associated with flushing when considered independently (38 of 68) than use ioxaglate (24 of 74)(P < 0.005, chi-square test). There was no difference in the incidence of cardiac events, or any combination of allergic-type adverse events, cardiac events, and flushing in patients who received iopamidol or ioxaglate. In this double-masked study, iopamidol caused fewer allergic-type adverse events (excluding flushing and cardiac events) but more flushing than ioxaglate in patients with a history of asthma or atopic disease. When cardiac events also were considered, there was no difference in the incidence of reactions after iopamidol and ioxaglate.