Peptides derived from digestion of wheat gluten, called exorphins, have been previously detected in urine samples from autistic subjects. Because of their opioid activity, they have been suggested by some as playing a role in the etiology of autism. Previous LC-MS results from our laboratories indicated that exorphins degrade rapidly in biological fluids in the absence of the protease inhibitor aprotinin. Here, we show that two of the exorphins, B4 and B5, can be detected in blood plasma samples of patients diagnosed with celiac disease (i.e. high intestinal permeability) using LC-MS/MS. Experiments were performed on a Thermo Electron Orbitrap mass spectrometer. The presence of exorphins in the plasma was monitored from samples collected up to 2 hrs. after the consumption of a pizza ("Pizza Test") by the subjects. The exorphins were detected in three of four test subjects by LC-MS/MS; MS/MS spectra prove conclusively that the peptides are indeed exorphins. This is the first time exorphins have been detected in blood plasma samples.