Countywide antibiotic resistance patterns may provide additional information from that obtained from national sampling or individual hospitals. We reviewed susceptibility patterns of selected bacterial strains isolated from blood in San Francisco County from January 1996 to March 1999. We found substantial hospital-to-hospital variability in proportional resistance to antibiotics in multiple organisms. This variability was not correlated with hospital indices such as number of intensive care unit or total beds, annual admissions, or average length of stay. We also found a significant increase in methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and proportional resistance to multiple antipseudomonal antibiotics. We describe the utility, difficulties, and limitations of countywide surveillance.