Ampicillin-resistant Haemophilus influenzae type B have been reported only during the past year. Five clinical isolates from the U.S. and Germany all had the TEM-type beta-lactamase which is known to be transferred widely among other gram-negative bacilli. Unlike those bacilli, however, the H. influenzae cell had very little barrier to entry of penicillins. This greater permeability of the H. influenzae cell to penicillins appeared to reduce the protective effect of its beta-lactamase, in that acquisition of the TEM-type beta-lactamase increased levels of resistance to penicillins much less for individual cells of H. influenzae than for those of Escherichia coli. Large inocula of either species appeared highly resistant. The unusually low level of resistance of individual cells of H. influenzae containing the TEM-type beta-lactamase may have delayed their emergence or recognition, and has unresolved clinical implications.