Continuous 12-year (1990--2001) focal surveillance of the antibiotic resistance among the most common nosocomial pathogens (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter sp., and Staphylococcus aureus) in 1325 Intensive Care Unit patients was performed. The surveillance period was divided in three 4-year time intervals (1990--1993, 1994--1997 and 1998--2001) and the prevalence of resistance was compared between intervals. Specimens included blood, urine and respiratory tract specimens. The incidence and trends of resistance to six antibiotics showed inconsistent results. Aminoglycoside resistance decreased among K. pneumoniae_isolates (gentamicin 83%, 72.7% and 49.6%; amikacin 50.9%, 51.5% and 18.2%) and Acinetobacter sp. strains (amikacin 77%, 63.4% and 58.2%) but increased in P. aeruginosa (amikacin 27.5%, 63.3% and 44.1%). Overall, resistance to ceftazidime, ciprofloxacin, and imipenem increased but imipenem resistance is still low, particularly among Acinetobacter sp. isolates (0, 2.1% and 1.5%). However, imipenem resistance increased among P. aeruginosa (10.2%, 31.6%, 22.1%). The prevalence of methicillin resistance was high but did not change during the surveillance period (82.3%, 78.3% and 82.2%). The present study suggests a complex picture of the development of antibiotic resistance in a single ICU. Significant changes occur over time but they are unpredictable and do not show identical tendencies for different species and antibiotics.