In a collaborative study involving five medical centers, 6% of 2,440 consecutive isolates of Enterobacteriaceae were resistant to cefoperazone; resistance to cefoperazone was reduced to < 1% by the addition of sulbactam. Susceptibility to cefoperazone and cefoperazone-sulbactam was accurately predicted by disk diffusion tests. Resistance to cefoperazone, however, was not as reliably detected by disk tests and results of dilution tests were not always consistent. The prevalence of resistance to cefoperazone and/or the ability to detect resistance had a significant influence on very major error rates for individual laboratories.