The inoculum effect (IE) is a laboratory phenomenon that is described as a significant increase in the minimal inhibitory concentration of an antibiotic when the number of organisms inoculated is increased. The IE generally occurs with beta-lactam antibiotics in relation to beta-lactamase-producing bacteria. An IE occurs with the first- and second-generation cephalosporins against Staphylococcus aureus and less often with the quinolones, beta-lactam-resistant penicillins, cefoxitin, and aminoglycosides. An IE occurs with the penicillins against the Enterobacteriaceae and Pseudomonas species, and a variable IE occurs with cephalosporins; however, no IE occurs with aminoglycosides, quinolones, imipenem, and chloramphenicol against these organisms. An IE occurs with beta-lactam antibiotics against Haemophilus influenzae and with the penicillins and the cephalosporins against penicillinase-producing Neisseria gonorrhoeae and Branhamella catarrhalis. An IE occurs with the penicillins and cephalosporins against the Bacteroides fragilis group; no IE occurs with cefoxitin and imipenem. Although certain antibiotics exhibit an IE, they are still capable of eradicating infections when administered appropriately. Thus, the clinical significance of this laboratory phenomenon has yet to be elucidated.