OBJECTIVE - Exposure to infections in infancy or childhood may be important in the pathogenesis of type 1 diabetes, but a protective role has also been suggested. We tested the hypothesis that increased early contact with infectious agents, measured by day care exposure, would decrease the risk of type 1 diabetes in childhood. RESEARCH DESIGN AND METHODS - We conducted a systematic review of case-control studies. Meta-analysis was performed to combine results, assess for heterogeneity, and explore variation in study design. RESULTS - Several generally well-designed case-control studies show a statistically significant protective effect of day care on type 1 diabetes. However, meta-analysis revealed too much heterogeneity to accept the overall synthesis results and none of the studies used prerecorded data. Day care does seem to have a protective effect in the subgroup of children who will be diagnosed with type 1 diabetes before the age of 5 years (odds ratio = 0.6, 95% CI 0.5-0.8); however, this result is based on only two studies. CONCLUSIONS - Recall bias is one alternate explanation for these data confirmation using prerecorded data is required. Such data could be prospectively measured in cohort studies of children at risk. We also suggest that information about day care attendance be measured in randomized trials of agents for the prevention of type 1 diabetes, as clay care exposure could potentially modify the effect of the preventive agent.