Objective: The aim of this work was to determine the effects of specific changes in the structure of 13C-labeled triglyceride (TG*) on its fecal excretion relative to total stool fat excretion determined simultaneously in patients with reduced exocrine pancreatic function. Methods: A series of 47 studies were conducted in 26 young cystic fibrosis (CF) patients and 11 adult patients with chronic pancreatitis over a five year period. Each test consisted of ingesting a single high fat test meal containing both 13C-labeled triglyceride (TG*) and dysprosium chloride (DyCl3) a nonabsorbable marker of intestinal transit; in most studies the food colorant brilliant blue (FD&C blue #1) was administered along with the DyCl3. The TG*s tested were: P*P*P* = TRIPALMITIN-1,1,1-13C3; SO*S = 2-OCTANOYL-1,3-DISTEARIN-2-octanoyl-1,2-13C2; and P*LP* = 2-LAURYL-1,3-DIPALMITIN-dipalmitoyl-1,1,2,2-13C4. Ingestion of the test meal was followed by collection of individual stools for at least 72 hours. Stools were analyzed for 13C-Excess (13C*), total fat, and Dy. Results: Excretion of P*LP* showed a high degree of linear correlation with stool fat (r2 = 0.924) over a wide-range of fecal fat values. Excretion of SO*S was also significantly correlated with stool fat, but its excretion was less than 10% at all levels of steatorrhea and the slope of the regression line relating TG* excretion to stool fat was some four to five times smaller than observed for P*LP*. Fecal excretion of P*P*P* was highly correlated with stool fat (r2 = 0.941) in patients with moderate steatorrhea (<25 g fat/24 hours) and the slope of the regression line (3.20) was considerably greater than for P*LP*. Only results from those studies in which stool collections were complete (Dy excretion >90%) were utilized in the statistical comparisons (36 of 47 studies). Conclusions: The observed highly significant linear correlation between P*LP* and stool fat over the entire range of steatorrhea suggests that P*LP* excretion may be a suitable surrogate for fecal fat in patients with reduced exocrine pancreatic function. Because fecal excretion of TG* administered as described can be accurately determined by sampling only two visually marked stools, development of a noninvasive test to replace the current 72-hour stool fat test using this approach is possible. Use of other engineered TG*s and/or labeled fatty acids, may provide a method for non-invasive in vivo assessment of the specific defect(s) leading to steatorrhea in other patient groups. © American 2003 College of Nutrition.