Five phase variants (PV1 to PV5) of the well-characterized, slime-producing, methicillin-resistant, pathogenic strain of Staphylococcus epidermidis sensu strictu RP62A (ATCC 35984) were isolated by the Congo red agar method. In comparison with the parent strain, the phase variants showed a different colonial morphology on Congo red agar, a strongly reduced adherence capacity, and decreased levels of resistance to methicillin, oxacillin, and penicillin. All phase variants yielded biochemical reaction patterns and profiles in pulsed-field gel electrophoresis identical to those of parent strain RP62A, indicating a common origin. All phase variants proved to have the capacity to shift back to the original phenotype of parent strain RP62A. A search for the resistance mechanisms of strain RP62A revealed P-lactamase production and the presence of mecA in PV1 to PV5 as well as parent strain RP62A. In Northem blots of total staphylococcal RNA, the phase variants showed no detectable mecA-specific transcription product, whereas parent strain RP62A revealed a strong signal, indicating that mecA transcription is not the mechanism responsible for the decreased methicillin resistance phenotype of phase variants PV1 to PV5.Staphylococcus epidermidis is recognized with increasing frequency as an opportunistic and nosocomial pathogen, particularly in association with infections of prosthetic devices and intravascular catheters. Several investigators have confirmed the presence of an extracellular polysaccharide matrix, called glycocalyx or slime, which is associated with adherence and accumulative growth on smooth surfaces and inhibition of host defenses (5,7,8,13,15,18,22,25,27).Many studies have suggested that slime production is one of the most important virulence factors in the pathogenicity of S. epidermidis (3,6,11,19,20,35). This adherence capacity is known to differ spontaneously among variants of the same parent strain (2-4, 9, 10). Christensen and coworkers (3) recently showed that slime production by S. epidermidis is not a stable phenomenon but undergoes phase variation. The ability to express different slime-producing phenotypes could provide the staphylococci with a greater degree of flexibility for colonizing a range of environments (2,3,9).Using a high-salt (6.5%), low-glucose medium (Memphis agar) for the detection of phenotypic variation, Christensen et al. (3) described phase variants RP62NA of the well-characterized strain RP62A (ATCC 35984). In comparison with the parent strain, the phase variants differed in their colonial morphologies and showed decreased levels of slime production and diminished virulence in a foreign body-associated model of endocarditis. Furthermore, the slime-negative phase variants that were isolated showed a remarkable increase in their susceptibilities to penicillin and oxacillin. This was determined by measuring in agar diffusion tests the mean zone of inhibition of the slime-negative phase variants compared with that of the parent strain, which is resistant to these antibiotics (3...