The spread of group A streptococcal infection to close contacts of infected persons is well recognized. With the resurgence of invasive group A streptococcal infections, there is an increased potential for clusters of patients with invasive disease. We reviewed data collected since December 1988 at the Centers for Disease Control (Atlanta) to identify clusters of infection in which one or more patients had invasive disease. Twelve family clusters were identified. Infection in index cases included the toxic shock-like syndrome and septicemia. Infection in family contacts included invasive infections, pharyngitis, or asymptomatic carriage. Most invasive disease occurred in adults, while the majority of noninvasive infections were in children. Five nosocomial clusters with spread of infection from patients to hospital personnel were documented. All index patients had the toxic shock-like syndrome; secondary infections included the toxic shock-like syndrome, pneumonia, bullous cellulitis, lymphangitis, and pharyngitis. Clusters of invasive infections also were identified in five nursing homes. Pneumonia, cutaneous infections, and the toxic shock-like syndrome occurred most commonly. Clustering by nursing home unit occurred in three outbreaks. In hospitals and nursing homes, improved infection control will likely decrease secondary spread; in families, spread of disease may be prevented by identifying and treating those harboring the organism or by chemoprophylaxis. Studies that characterize the rate of secondary infection are needed before definitive recommendations can be made.