Four household-based, randomized clinical trials, two each of zanamivir and oseltamivir, were designed primarily to estimate the effect of postexposure prophylaxis on preventing influenza illness in household contacts. However, the effect of influenza antivirals on infectiousness as well as on the ability of the virus to cause disease--the pathogenicity--have important public health consequences. The authors show how such studies can provide estimates of pathogenicity, antiviral efficacy for pathogenicity, and the antiviral effect on infectiousness. Analysis of the four studies confirmed the high prophylactic efficacy against illness of both zanamivir (75%, 95% confidence interval (CI): 54, 86) and oseltamivir (81%, 95% CI: 35, 94). The effect on reducing infectiousness was 19% (95% CI: -160, 75) for zanamivir and 80% (95% CI: 43, 93) for oseltamivir. Pathogenicity in controls ranged from 44% (95% CI: 33, 55) to 66% (95% CI: 48, 72). Efficacy in reducing pathogenicity for zanamivir was 52% (95% CI: 19, 72) and 56% (95% CI: 14, 77) in the two studies; for oseltamivir, it was 56% (95% CI: 10, 73) and 79% (95% CI: 45, 92). Studies of influenza antivirals in transmission units would be improved if randomization schemes were used that allow estimation of the antiviral effect on infectiousness from individual studies.