As antimicrobial resistance among Gram-positive species becomes more common, alternative agents need to be developed for the therapy of serious infections. SCH 27899 is a compound from the everninomicin class of antimicrobial agents that possesses a potent Gram-positive spectrum. We evaluated three disk concentrations (0.25, 1, and 5 micrograms) of three SCH 27899 formulations including SCH 27899 base (SCHB), N-methylglucamine SCH 27899 (NMG-SCH), and NMG-SCH complexed with hydroxypropyl beta-cyclodextrin. Disk zone diameters were correlated with minimum inhibitory concentration for 209 aerobic, nonfastidious Gram-positive strains and selected Gram-negative bacilli to develop disk diffusion interpretive criteria. No significant differences in activity were noted among the three SCH 27899 preparations. Of the three disk concentrations, the correlation coefficient was greatest (r = 0.88) for the 5-micrograms SCHB disk test. For a tentative break point of < or = 2 micrograms SCHB/ml, preliminary disk interpretive criteria were: susceptible at > or = 12 mm, intermediate at 10-11 mm, and resistant at < or = 9 mm (absolute categorical agreement, 99.5%). Zones were small secondary to drug solubility and diffusion limitations. Using these criteria for the SCHB 5-micrograms disks, nearly all of the tested Gram-positive organisms were susceptible including methicillin-resistant staphylococci and vancomycin-resistant enterococci.