Synergy, determined by isobolograms constructed from the minimal inhibitory concentrations of combinations of ampicillin and chloramphenicol, was observed against six of 13 ampicillin-susceptible Haemophilus influenzae type b isolates and against five of eight ampicillin-resistant strains by using a small inoculum of 10(4) colony forming units (CFU) per milliliter. Synergy occurred against nine of 13 ampicillin-susceptible and against two of eight ampicillin-resistant strains using a large inoculum of 10(7) CFU/ml. When synergy was not observed, additive effects occurred against the remainder of isolates. Additive effects were also observed against single strains of chloramphenicol-resistant, nontypeable H. influenzae and H. parainfluenzae. No antagonism was observed. These data indicate that ampicillin and chloramphenicol may be synergistic against a significant number of H. influenzae strains depending on inoculum size, but the effect is unpredictable for a given isolate. These data support the recommendation that ampicillin and chloramphenicol both be used as initial therapy for patients with suspected bacterial meningitis.