Group A Streptococcus (GAS) causes common childhood diseases such as streptococcal pharyngitis and impetigo and can cause severe, life-threatening invasive disease including streptococcal toxic-shock syndrome and necrotizing fasciitis. Invasive GAS disease occurs when GAS infects a normally sterile site. Clusters of invasive GAS infection previously had not been reported among children in school or childcare centers (CCCs). However, on February 13, 1997, the Boston Public Health Commission received reports of cases of concurrent invasive GAS and varicella infection among two of 14 children in the same CCC classroom. Because of the potential for further spread of invasive disease, the Boston Public Health Commission initiated an investigation of these cases. This report describes the findings of the investigation, including risk factors for infection, and recommended prevention measures. The findings indicate the potential for widespread GAS infection and carriage in CCCs and suggest that, in this outbreak, antecedent use of varicella vaccine would have prevented cases of invasive GAS.