Methicillin resistance in staphylococci is primarily due to the methicillin resistance determinant, which produces an additional low-affinity penicillin-binding protein (PBP), PBP2′. Expression of PBP2′ is controlled by its own regulatory element and has the same induction system as the β-lactamases. Methicillin resistance levels do not, however, correlate with the amount of PBP2′ produced and are determined by chromosomal genes. Methicillin resistance in clinical isolates that do not contain the methicillin resistance determinant, and therefore do not produce PBP2′, is due to changes in the amount and/or affinity of the cells’ own PBPs, to penicillinase hyperproduction against a specific genetic background, or to synthesis of a meth