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To identify characteristic clinical manifestations and potential risk factors for invasive group A streptococcal (GAS) disease in children with varicella.A case-control study was conducted in Los Angeles and Orange Counties, CA. Cases were children with varicella who developed invasive GAS disease between January 1 and May 3, 1994 (n = 25). Controls were acquaintance, neighborhood or schoolmate children with uncomplicated varicella during the study period (n = 62). Cases were compared with controls with regard to underlying illness, child care practices, parental home health practices, health care-seeking behaviors, sociodemographic characteristics and clinical characteristics.Controlling for age we found that cases were more likely than controls: (1) to be cared for in the home vs. out-of-home child care (odds ratio (OR), 4.4 (95% confidence interval (95% CI), 1.1 to 17)); (2) to report having asthma (OR, 6.2 (95% CI, 1.2 to 41.0)) and to be taking albuterol (OR, 11.6 ((95% CI, 1.0 to 581)); (3) to be secondary varicella cases within a household (OR, 7.3 (95% CI, 2.2 to 25)); (4) to report fever after Day 2 of varicella; and (5) to have contacted their health care provider later than controls (Day 3.8 rather than Day 1.7, P < 0.001).To our knowledge this is the first case-control study exploring potential risk factors for invasive GAS disease in children with varicella. Both previously healthy children with varicella and those with underlying medical problems, including asthma, may be at increased risk for GAS complications. Interventions should be targeted to parents and health care providers to increase awareness of early signs and symptoms of invasive GAS disease in children with varicella. Additional studies are needed to confirm the associations suggested by this study between GAS complications of varicella and asthma, in-home child care, secondary vs. primary varicella household cases and delayed contact with medical care providers.