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Immunologic abnormalities have been described recently in patients with cystic fibrosis (CF). We have evaluated local IgA production by jejunal mucosa in vitro in seven patients with CF, seven patients with hereditary pancreatitis (HP), and 29 normal subjects. IgA synthesis in biopsy specimens was assessed by measuring 14C-L-leucine incorporation into IgA. Pancreatic enzymes were absent in all CF patients, and in two of seven HP patients; in four HP patients enzyme levels were reduced to 20% of normal. The mean IgA incorporation value in CF patients was 20,373 ± 9,244 cpm/mg protein (mean ± SD), and in HP patients was 11,403 ± 4,585, both values significantly greater than normal (6,688 ± 2,449) (p µ 0.001). In addition, the mean IgA incorporation value in CF patients was greater than the value in HP patients. (p µ 0.05). Within each patient group there was no correlation between IgA incorporation values and serum IgA levels, age, Shwachman score, severity of lung disease, type of bacteria in sputum cultures, or roentgenographic abnormalities of the small bowel. The most reasonable explanation for the findings is that patients with CF and HP are under an increased local antigenic stimulus, perhaps due to an altered gastrointestinal environment which leads to increased local IgA production.