On the basis of the MICs of methicillin and oxacillin, 975 clinical isolates of Staphylococcus aureus were categorized as having resistance, borderline susceptibility or full susceptibility to penicillinase-resistant penicillins (PRPs). The borderline phenotype accounted for 122 isolates (12.5%), whereas 562 isolates were fully susceptible and 290 resistant; one remaining isolate had resistance to methicillin and borderline susceptibility to oxacillin. Reductions in the MICs of methicillin and oxacillin in the presence of sulbactam were greater in strains with borderline PRP susceptibility than in fully susceptible or resistant isolates. Over 99% of fully PRP-susceptible strains, 93% with borderline susceptibility and 71% of resistant strains were susceptible to ampicillin/sulbactam. The production of beta-lactamase, assayed in all strains using nitrocefin as substrate, could be detected without prior induction in 729 strains and after induction only in another 156 strains. With only two exceptions, the beta-lactamase negative strains were part of the fully PRP-susceptible group of organisms (88 of 562 isolates). Among the borderline isolates, strong beta-lactamase reactions were encountered with particular frequency, but not in all strains and not exclusively in borderline strains. Although associated with the majority of borderline strains, beta-lactamase hyperproduction thus did not appear to be an essential feature of the borderline phenotype. The results obtained may have implications for laboratory and clinical medicine, also in the light of recent findings suggesting that other mechanisms besides beta-lactamase hyperproduction may account for borderline susceptibility to PRPs.