Pls, the surface protein of methicillin-resistant Staphylococcus aureus (MRSA), prevents adhesion of clinical strain 1061 to immobilized fibronectin (Fn) and immunoglobulin G (IgG). Invasion of mammalian cells by S. aureus depends on Fn-mediated binding of staphylococcal Fn-binding proteins to host cell beta (1)-integrins. In the present study, we show that, for 10 clinical Pls-positive (Pls(+)) MRSA strains, adhesion to immobilized Fn, fibrinogen (Fg), IgG, and laminin, as well as binding to soluble Fn and Fg, was less efficient than adhesion and binding associated with 4 Pls-negative (Pls(-)) MRSA strains. However, binding to soluble IgG was comparable among both types of strains. For 293 cells, Pls(+) strains were less invasive than were Pls(-) strains (median [range], 35% [22%-70%] and 110% [89%-141%], respectively, compared with strain Cowan 1). Disruption of the pls gene of strain 1061 increased invasiveness, but it did not affect binding of soluble Fn, Fg, and IgG. Complementation restored the low level of invasiveness, but it did not restore the low level of adhesion to immobilized Fn. In conclusion, the reduced adhesiveness and invasiveness of MRSA appear to generally correlate with expression of Pls.