Bile acid, lysolecithin, fatty acid, and lecithin are four duodenal lipids which may cause or modify gastric mucosal injury. We determined total and soluble concentrations of these lipids in gastric aspirates from 9 subjects with Billroth II (B-II) anastomosis and 5 normal controls. To assess injurious potential, each lipid was tested for capacity to disrupt the gastric mucosal barrier in canine Heidenhain pouches. Minimal injurious levels were ~2.5 mM for bile acid and 0.2-0.4 mM for lysolecithin. Neither fatty acid nor lecithin disrupted the barrier or modified injury by bile acid or lysolecithin. No normal subject had intragastric concentrations of bile acid or lysolecithin in the injurious range. During fasting, B-II subjects had a median concentration (millimolar) for total bile acid of 4.24 and for lysolecithin of 0.33. Corresponding median concentration of soluble bile acid was 2.49 and that of lysolecithin was 0.26, both significantly below total levels (P < 0.004 and < 0.02, respectively). Eating lowered median total concentration of bile acid (1.58, P < 0.008), but not lysolecithin (0.29). After eating, median soluble concentrations of both bile acid (0.76) and lysolecithin (0.02) were lower than corresponding fasting levels (P < 0.02 and < 0.04, respectively). Three B-II subjects had fasting soluble levels of bile acid and lysolecithin clearly in the injurious range. In the postprandial state, however, only 1 subject had soluble levels of bile acid and lysolecithin in the toxic range. Thus even in the absence of a pyloric sphincter, few subjects continuously maintain soluble intragastric concentrations of duodenal lipids above the injurious level.