BACKGROUND: Acute respiratory tract infections (ARTIs) are a major cause of childhood morbidity and mortality. Immunostimulants (IS) may reduce the incidence of ARTIs. OBJECTIVES: To determine the efficacy and safety of IS in preventing ARTIs in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005); MEDLINE (January 1966 to January 2006); and EMBASE (January 1990 to January 2006); PASCAL (up to January 2006); SciSearch (up to January 2006); and IPA (up to January 2006) for reports of trials. Investigators in the field were also contacted. Ongoing studies were searched in the trial registration web site, metaRegister of Controlled Trials. SELECTION CRITERIA: All comparative trials which enrolled patients less than 18 years of age were included. The intervention of interest was the use of an IS medication administered by any method for preventing ARTIs. Clinical trials using random or quasi-random allocation and comparing IS medication or medications to placebo were included. DATA COLLECTION AND ANALYSIS: The outcome on ARTIs was analyzed both as the mean number of ARTIs by group and as a percent change in the rate of ARTIs. Meta-analysis was undertaken using a random-effects model and results were presented as weighted mean differences (WMD) with 95% confidence intervals (CI). The trials search, quality assessment and data extraction were undertaken independently by two authors. A funnel plot suggested there may be publication bias in the trials identified. MAIN RESULTS: Thirty-four placebo controlled trials (3877 participants) provided data in a form suitable for inclusion in the meta-analysis. When compared with placebo, the use of IS was shown to reduce ARTIs measured as the total numbers of ARTIs (WMD -1.27; 95% CI -1.58 to -0.97) and the difference in ARTIs rates (WMD -39.68%; 95% CI -47.27% to -32.09%). The trial quality was generally poor and a high level of statistical heterogeneity was evident. The subgroup analysis of bacterial IS studies produced similar results, with lower heterogeneity. No difference in adverse events was evident between the placebo and IS groups AUTHORS' CONCLUSIONS: This review showed that IS reduces the incidence of ARTIs in children, by 40% on average. However, due to significant heterogeneity and the poor quality of the trials this positive result should be interpreted with caution. The safety profile of IS appears to be good. Further high-quality trials are needed and we encourage national health authorities to conduct large, multicenter, double-blind, placebo-controlled trials on the role of IS in the prevention of ARTIs.