. Thirty-five subjects completed the study. The mean similarity percentages of TGGE profiles between baseline and each treatment day sample were significantly lower for the ampicillin group than for the group receiving ampicillin plus P1A recombinant -lactamase on days 3, 4, and 5 (P < 0.001). Compared with the ampicillin group, subjects receiving ampicillin plus P1A recombinant -lactamase had significantly fewer ampicillin-resistant coliforms on days 3, 4, and 5 and at follow-up (P < 0.001) and fewer TEM -lactamase genes on days 3, 4, and 5 (P < 0.02). P1A recombinant -lactamase was safe and well tolerated. In healthy subjects, P1A recombinant -lactamase prevents ampicillin-induced alterations in intestinal microflora, emergence of resistance, and the number of TEM genes.