An ongoing registration of resistance patterns of microorganisms in a large area in the Netherlands demonstrated a slow but steady increase of resistance to several antibacterials in the past ten years. For some bacteria and for some selected antimicrobial agents this increase was such that it might no longer be justifiable to choose them for empirical therapy. For Escherichia coli, resistance increased from 14% in 1982 to 28% in 1992 for co-trimoxazole and for trimethoprim, and from 24% to 34% for amoxycillin. For nitrofurantoin the figures were 1–5% and 4–0%, respectively. Comparison with other areas in the Netherlands showed similar results, so it can be considered a nationwide problem which may have consequences for national antibiotic guidelines for the treatment of infections.