A double blind, randomized clinical trial compared loracarbef (LY163892) with penicillin VK. Two hundred thirty-three pediatric patients (less than or equal to 12 years) with a diagnosis of pharyngitis or tonsillitis resulting from Group A beta-hemolytic streptococci were randomized to treatment. Patients in the loracarbef group (n = 120) received loracarbef as a 15-mg/kg/day oral suspension or 200-mg capsule taken twice daily for 10 days. Patients in the penicillin group (n = 113) received penicillin VK as a 20-mg/kg/day oral suspension or 250-mg capsule taken four times daily for 10 days. Successful clinical responses were demonstrated in 101 of the 104 (97.1%) evaluable patients treated with loracarbef compared with 83 of 88 (94.3%) of evaluable patients treated with penicillin. The clinical relapse rate for the loracarbef group was 2.9% vs. 5.7% for the penicillin group. Bacteriologic response data approximated the clinical response data, as eradication of Group A beta-hemolytic streptococci was found in 86.5 and 81.8% of the loracarbef group and the penicillin group, respectively. No statistically significant difference in the incidence of treatment-emergent adverse reactions was noted between the two groups. The results indicate that loracarbef taken twice daily was comparable in safety and efficacy to penicillin VK taken four times daily in the treatment of Group A beta-hemolytic Streptococcus-associated pharyngitis and tonsillitis in children.