The effects of oral enzyme replacement therapy on breath hydrogen excretion and symptoms after milk ingestion were studied in lactase-deficient patients. Sixteen symptomatic patients underwent interval hydrogen breath tests using whole milk as substrate. Each study was repeated with the addition of 250 mg of beta-D-galactosidase derived from Aspergillus oryzae (Lactrase) given orally with the milk. Subsequently seven of those 11 patients who did not normalize their hydrogen excretion with 250 mg of Lactrase were available to be restudied with a 500-mg dose. Mean cumulative and peak hydrogen excretions were calculated for the baseline (milk alone), 250 mg, and 500 mg Lactrase groups. Significant (p less than or equal to 0.05) decreases in cumulative and peak hydrogen excretion were noted between the 500 mg Lactrase versus the baseline group, but not between the 250 mg versus baseline group. Five of the 16 (31%) symptomatic lactase-deficient patients normalized their hydrogen excretion after 250 mg of Lactrase; four of seven (57%) who had not normalized on 250 mg, normalized their hydrogen excretion with 500 mg of Lactrase. A different pattern was observed in the incidence of symptoms. Five of the nine patients (56%) whose hydrogen excretion normalized with the addition of Lactrase at either dosage became asymptomatic after milk ingestion; in addition, three patients who did not normalize their hydrogen also became asymptomatic. We conclude that oral Lactrase in sufficient dosage temporarily reverses lactose malabsorption in some patients.