People who are sensitive to wheat-based products have been reported to be more tolerant to spelt wheat. A comparative study to investigate the immuno-reactivity of human IgE against wheat and spelt antigens was carried out using the blood sera from the Geelong Osteoporosis Study (GOS) patients who have previously been identified with raised anti IgE against wheat by Phadia RAST ImmunoCAP. Since the Phadia wheat and spelt antigens provided originated from Europe, Australian wheat and spelt varieties were also used to prepare antigens in order to investigate the response of Australian sera to local wheats. 73 patients with raised IgE response against wheat and 6 control patients were used in these analyses. Of these 63% (n=50) showed a higher IgE immuno-reactivity against EU wheat, while 30% (n=24) showed higher IgE response against EU spelt antigens, the remaining 7% have indifferent responses against both antigens. The comparison between the Phadia EU antigens and streptavidin coupled Australian antigen extracts showed good correlation (r2 = 0.91 for wheat and r2=0.88 for spelt respectively). This has allowed the data derived using coupled Australian streptavidin antigen caps to be normalised with the Phadia EU antigen caps. In 73 out of 79 (92%) IgE wheat positive sera RAST tested against Australian wheat and spelt, the spelt immuno-reactivity was significantly lower than wheat. The results we have found show that the immuno-reactivity of IgE wheat positive sera from a normal Australian population is lower for spelts compared to wheats regardless of their origin but much lower against Australian spelt than EU spelt. A clinical feeding trial would be necessary to confirm if this difference in immuno-reactivity between spelt and wheat is consistent with a difference in allergenicity.