Group C beta-hemolytic streptococci cause rare epidemic outbreaks of pharyngitis, but their role in sporadic endemic pharyngitis has been uncertain. We addressed the question of whether non-group A beta-hemolytic streptococci are associated with endemic pharyngitis in two ways. First, we compared rates of isolation from throat swabs of group A, B, C, and G and ungrouped beta-hemolytic streptococci ("culture negative") in adult patients vs those rates in controls. Second, we collected in standardized form clinical indexes of patients with pharyngitis: signs and symptoms graded for severity, the examining physician's subjective estimate of the probability of streptococcal pharyngitis, a logistic regression score predicting streptococcal pharyngitis, and whether antibiotic therapy was prescribed. After collecting data and cultures on 1425 patients with sore throats and cultures on 284 controls, we found the following: group C streptococci were isolated significantly more frequently in patients with sore throats than in controls (6% vs 1.4%); four clinical signs and two symptoms distinguished group C-associated pharyngitis as more severe than culture-negative pharyngitis; and six clinical signs and one symptom distinguished group C-associated pharyngitis as less severe than group A pharyngitis. Physicians' subjective estimates, logistic regression scores, and antibiotic treatment all characterized group C-associated pharyngitis as more severe than culture-negative sore throats but less severe than group A pharyngitis. From these data we present the first definitive evidence that group C streptococci are associated with endemic pharyngitis, show that clinical presentation distinguishes a group of patients with group C-associated pharyngitis from populations with culture-negative sore throats and from those with group A pharyngitis. Physicians' response to that presentation merits consideration in the context of rapid group-specific diagnosis of streptococcal pharyngitis by group A antigen tests.