The evolution of clarithromycin, metronidazole and amoxycillin resistance in 246 Spanish Helicobacter pylori clinical isolates, obtained from paediatric patients during a 9 year period, was determined by an agar dilution technique. Clarithromycin resistance (MIC 1 mg/L) was 2.27% (IC95 0.05-12.02) in 1991-1993, 20.98% (IC95 12.72-31.46) in 1994-1996 and 28.33% (IC95 20.48-37.28) in 1997-1999 (P < 0.01). Metronidazole resistance (MIC 8 mg/L) was 7.14% (IC95 1.49-19.48) in 1991-1993, 20.25% (IC95 12.04-30.79) in 1994-1996 and 43.90% (IC95 32.95-55.30) in 1997-1999 (P < 0.01). Amoxycillin resistance was not found (all strains showed MICs < 2 mg/L).