OBJECTIVE: The purpose of this work was to investigate the association between infections in the first 2 years and subsequent diagnosis of autism spectrum disorders. METHODS: We conducted a case-control study among children born at Kaiser Permanente Northern California from 1995 to 1999. Case subjects (n = 403) were children with an autism diagnosis recorded in Kaiser Permanente databases. Control subjects (n = 2100) were randomly sampled from the remaining children without autism and frequency matched to case subjects on gender, birth year, and birth hospital. Information on infections and covariates were obtained from Kaiser Permanente and birth certificate databases. RESULTS: Overall, infection diagnoses in the first 2 years of life were recorded slightly less often for children with autism than control children (95.0% vs 97.5%). Among specific diagnoses, upper respiratory infections were significantly less frequently diagnosed and genitourinary infections more frequently diagnosed in children with autism. In the first 30 days of life, the frequency of having an infection was slightly higher among children with autism (22.6% vs 18.7%). CONCLUSIONS: Children with subsequent diagnoses of autism do not have more overall infections in the first 2 years of life than children without autism. Data suggest that children with autism may have modestly elevated rates of infection in the first 30 days and that, during the first 2 years, children with autism may be at higher risk for certain types of infections and lower risk for others. Additional studies that explore the associations between prenatal and early childhood infections and autism may help clarify the role of infection and the immune system in the etiology of autism spectrum disorder.