Escherichia coli ATCC 12407 was exposed in an in-vitro kinetic model to multiple dose ampicillin regimens differing in simulated drug elimination half-life but with equal dosage intervals and similar dose levels. Bacterial sensitivity was monitored during drug exposure. Greater bactericidal effect was observed with long half-life regimens. The development of rapid low-level resistance was not influenced by the half-life. Results suggest that in-vivo drug activity may be improved by increasing the drug elimination half-life.