As antimicrobial resistance among Grain-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 mu g) 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 Grain-positive stains 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-mu g SCHB disk test. For a tentative break point of less than or equal to 2 mu g SCHB/ml, preliminary disk interpretive criteria were: susceptible at greater than or equal to 12 mm, intermediate at 10-11 mm, and resistant at less than or equal to 9 mm (absolute categorical agreement, 99.5%). Zones were small secondary to drug solubility and diffusion limitations. Using these criteria for the SCHB 5-mu g disks, nearly all of the tested Gram-positive organisms were susceptible including methicillin-resistant staphylococci and vancomycin-resistant enterococci.