Seventeen children with cystic fibrosis were studied in a 6-week double-blind, placebo-controlled, crossover trial to determine the efficacy of misoprostol, 100 micrograms, four times a day, in improving fat absorption in patients already on pancreatic enzyme therapy. In those patients who had greater than 90% absorption on enzyme therapy alone, no further significant increase in absorption was achieved with misoprostol administration. Those patients who had absorption of less than 90% on standard enzyme therapy showed a significant improvement with misoprostol administration (p less than 0.01). One patient had a significant elevation in the eosinophil count during the period of misoprostol administration, but there were no significant changes in any other hematological or biochemical parameter. Misoprostol appears to be of benefit to those children with cystic fibrosis who have residual malabsorption on standard enzyme therapy.