One notable consequence of synergy is that the antiviral activities of each drug in the combination is enhanced compared to the activities of the drugs as single agents. To demonstrate this, we compared the antiviral activity of each of the three drugsamantadine, ribavirin, and oseltamivir carboxylate -as single agents and in the presence of fixed concentrations of the second and third drugs against CA10 replication. For each drug, the EC 50 was reduced in triple combination compared to the EC 50 as a single agent, indicative that each drug was active at lower concentrations (greater potency). For example, the EC 50 for amantadine as a single agent was reduced by 3.2-fold in combination with 1 mg/mL ribavirin and 0.0032 mg/mL oseltamivir carboxylate; the EC 50 for ribavirin as a single agent was reduced by 2.7-fold in combination with 0.0032 mg/mL oseltamivir carboxylate and 1 mg/mL amantadine; and the EC 50 for oseltamivir carboxylate as a single agent was reduced 16.2-fold in combination with 1 mg/mL ribavirin and 1 mg/mL amantadine ( Table 2) . For all three drugs, the reduction in EC 50 values observed in the triple combination compared to the single agent was statistically significant (P,0.05), indicative that each drug had greater antiviral potency and was effective at lower concentrations. In addition, the EC 50 of all three drugs in triple combination were reduced 1.5-to 6.5-fold compared to the EC 50 in double combinations, indicative of that the antiviral activity of the drugs in triple combination were enhanced compared to double combinations. Importantly, the data presented here do not represent the maximum reductions in EC 50 values for the three drugs. Due to the dynamic range of the assay, we were only able to obtain precise dose-response curves for each drug at fixed concentrations of the second and third drugs which were well below their EC 50 values and well below concentrations where maximum synergy occurred. At higher concentrations, the antiviral activity of the second and third drug contributed significantly to the inhibition, which decreased the linear range of the assay and reduced the accuracy of the curve-fitting (data not shown). A comprehensive assessment of the interaction of two or three drugs in combination requires the evaluation of multiple concentrations of each drug in order to quantify synergy over the entire dosing range, as was done in the section above.