The validity of pancreatic enzyme substitution therapy in the two months following diagnosis of celiac disease was investigated. Twenty patients (8 males, 12 females), mean age 14.2 months (group A) received an enzyme substitution preparation. The control group (group B) included 20 patients (9 males, 11 females), mean age 14.5 months, treated with placebo. Before starting treatment, we performed a stratification for age, weight-for-age at diagnosis, and degree of pancreatic insufficiency. The therapies were then administered randomly in double-blind fashion. On diagnosis and 30 and 60 days after commencement of a gluten-free diet with identical calorie intake in both groups, a series of anthropometric variables were determined. After 30 days weight increase in group A patients was significantly higher (in grams) than in group B: 1131 +/- 461 vs 732 +/- 399 (P < 0.006). Weight-for-age increase also was greater in group A than in group B: 9.2 +/- 5.1% vs 5.0 +/- 4.0% (P < 0.002). The increase in height Z score, weight-for-height, arm circumference, and subscapular and tricipital fold measurements were greater in group A patients than those in group B, but the difference was not significant. After 60 days of therapy none of the parameters considered were significantly different in the two groups. We concluded that pancreatic enzyme therapy is certainly useful in the first 30 days after diagnosis of celiac disease.