Does scaling up of malaria control by combining indoor residual spraying (IRS) and long-lasting insecticidal nets (LLIN) enhance protection to populations? Results from a literature search and from recent household surveys in Bioko, Equatorial Guinea, and Zambezia, Mozambique are presented. Five out of eight previous studies reported a reduced risk of infection in those protected by both interventions compared with one intervention alone. Surveys in Bioko and Zambezia showed strong evidence of a protective effect of IRS combined with nets relative to IRS alone (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.59-0.86 for Bioko, and OR = 0.63, 95% CI = 0.50-0.79, for Zambezia). The effect of both interventions combined, compared with those who had neither, was OR = 0.46, (95% CI = 0.76-0.81) in Bioko and 0.34 (95% CI = 0.21-0.56) in Zambezia. Although the effects of confounding cannot be excluded, these results provide encouragement that the additional resources for combining IRS and LLIN are justified.