The in vitro activity of cefixime against 2,458 clinical isolates of Haemophilus influenzae was determined. All the strains were inhibited by less than or equal to 2 micrograms of cefixime per ml, and the modal MIC was 0.03 micrograms/ml. Activity was unaffected by the presence of beta-lactamase produced by 157 isolates. Nineteen of the twenty-four isolates for which cefixime MICs were greater than or equal to 0.5 micrograms/ml were beta-lactamase negative but showed reduced susceptibility to ampicillin.