Following determination of MICs and MBCs of spiramycin and trimethoprim by the broth microdilution method for 16 typable (including 13 type b) and 15 nontypable H. influenzae isolates, bactericidal synergy was tested by the chequerboard method and the time-kill curve methods. Nineteen (13 typable and six nontypable) of 31 strains demonstrated synergy by the chequerboard method. Ten strains showed indifference, and two manifested antagonism. In contrast, 12/13 strains tested by the time-kill method showed synergy and 1/13 demonstrated indifference. Of note was the finding that seven isolates that showed indifference by chequerboard method (three typable, four nontypable) manifested synergism by the kill-curve method. Of the two nontypable strains showing antagonism by chequerboard, one manifested synergy and the other indifference by the time-kill method. Our studies show that in-vitro synergy between spiramycin and trimethoprim against H. influenzae strains is frequently demonstrable. In-vivo studies may be helpful in confirming these in-vitro observations.