Objective: Optimal [C-13]-urea breath test (UBT) conditions for diagnosis of Helicobacter pylori infection are still being fine-tuned. In the present study we investigated the impact of delaying gastric emptying by different meal substrates or L-DOPA, a drug known to induce gastric stasis, on the performance of the [C-13]-UBT. Methods: A total of 115 patients participated in the study. On two consecutive days, participants ingested [C-13]-urea (100 mg) 10 min after either 270 ml of a mixed formula meal (1 Kcal/ml) or an equivalent amount of tap water. In 11 participants two additional tests were performed with or without oral 500 mg L-DOPA given 30 min before [C-13]-urea load. The C-13/C-12 ratio in a basal breath sample was compared with ratios in samples collected 30 and 60 min after [C-13]-urea. Histological assessment of H. pylori presence in antral biopsy served as reference standard. Results: Formula UBT showed excellent specificity (100% at 30 and 60 min) and good sensitivity (97% at both time intervals), whereas water UBT had the same specificity but slightly lower sensitivity (94% at 30 min and 73% at 60 min). In formula UBT,C-13/C-12 ratios were higher at 60 min than at 30 min (21.7 +/- 2 vs 17.7 +/- 1.8 parts per thousand respectively, p < 0.01, whereas in water UBT C-13/C-12 ratios were higher at 30 min than at 60 min (13.9 +/- 1.5 vs 8.4 +/- 0.09 parts per thousand respectively, p < 0.01), Pretreatment with L-DOPA did not modify either the sensitivity or the specificity of the UBT. Conclusions: The performance of the [C-13]-urea with a formula meal may not be improved by pharmacologically delaying gastric emptying. A short, waterbased test may be a sensible approach to worldwide standardization of the [C-13]-UBT for H. pylori infection. (Am J Gastroenterol 1999;94:369-373. (C) 1999 by Am. Cell. of Gastroenterology).