The effect of inoculum size of five clinical isolates of Staphylococcus aureus and Escherichia coli on the activity of six antibiotics was studied. Cefoperazone and cefotaxime exhibited a large inoculum size effect with the studied strains. Amikacin, gentamicin, ofloxacin, and ciprofloxacin exhibited a rapid bactericidal activity and a minimal inoculum size effect. The inoculum size markedly affected the antibacterial activity of all the studied antibiotics against the clinical isolates studied. This inoculum size effect was more pronounced towards Escherichia coli than Staphylococcus aureus.