Background: Endoscopic forceps biopsy is a time-consuming process. Most of the time is spent by introducing the forceps through the endoscope channel, by withdrawing it and by removing the sample from the forceps. To save time we aimed at taking two biopsies before extracting the forceps (double bite biopsy=DBB). The purpose of this study was to compare the sample size of a single biopsy (SB) with the sample size of a DBB. As a means to quantify the relative sample size the protein content of the biopsies was determined. Materials and Methods: 79 SBs and 79 DBBs from the following segments of the gastrointestinal tract have been obtained during endoscopy in 79 patients after informed consent: rectum (30), sigma (9), colon (9), duodenum (3), antrum (10), and corpus (18). The following different types of forceps have been used: Olympus FB-24 U with a spike, 24K-1 with spike, FB-24Q-1 with spike, FB-24U, FB-28U, FB-25K, FB- 53U-1,Fujinon K2416RP, and K2418RP. In each patient a set of SB and DBB has been performed in random order. In 19/79 patients for the sets of SB and DBB spiked forceps have been used. The samples were processed using CytoLyt Solution (Boxborough, MA) as a transport medium and washing agent to lyse blood, dissolve mucus, and remove extracellular protein. The relative quantity of tissue of each specimen was evaluated by the colorimetric measurement of the protein concentration according to the Lowry assay. Results: Overall DBB increased the average protein content by 43% (p<0,01); in 66 % of the patients two particles were obtained by DB. With the spiked forceps two particles were obtained in all cases corresponding to an increase of protein content of 38%. With the unspiked forceps type in 52 % of the cases two particles were obtained, corresponding to an increase of protein content of 45%. Conclusions: DBB increased the amount of tissue obtained by 43% on average, when compared to SB. Whereas forcepses with a spike yielded a double sample in every case, conventional forcepses still provided an increased amount of tissue (by 18%). Further studies are required to evaluate whether the the sample size obtained by double biopsy suffices for histologic assessement of the specimen.