When safflower oil (triglyceride) was consumed without pancreatic enzymes by children with cystic fibrosis (CF), there was no rise in mean plasma linoleic acid levels over the next 4 h. When linoleic acid monoglyceride (LAM) was consumed, the increase in plasma linoleic acid levels was significantly greater than for safflower oil at 2 (p < 0.02), 3 (p < 0.01), and 4 h (p < 0.01). When free fatty acid (hydrolyzed safflower oil) was ingested, there was almost no increase in plasma linoleic acid levels in CF or control children. The absorption of linoleic acid from triglyceride, but not from LAM, was greater when the CF children also took pancreatic enzymes. Three children with CF had greater increases in plasma linoleic acid levels following ingestion of safflower oil when they took antacid and cimetidine with their pancreatic capsules, compared to when they only took the pancreatic capsules.