We compared the efficacy and safety of amoxicillin 1 g b.i.d. for 6 days and penicillin V 1 MU t.i.d. for 10 days in the treatment of group A beta-haemolytic streptococcal (GABHS) tonsillitis in adults. 342 patients with acute tonsillitis and a positive test for streptococcal antigen were included in a multicentre, randomized, open-label study; 338 patients were evaluable in an intention-to-treat analysis, and 234 with a positive throat swab culture in a per-protocol analysis. In the per-protocol analysis, the GABHS eradication rate at the end of treatment was comparable in the two groups: 92% (115/125) on amoxicillin and 92.7% (101/109) on penicillin (p = 0.95), as were the clinical success rates of 96% and 95.4%, respectively (p = 0.92). At the follow-up visit (day 28-32), 90.8% of patients treated with amoxicillin and 92.6% of those treated with penicillin V were free of GABHS (p = 0.85). Sore throat disappeared significantly faster on day 2 (p = 0.039) in the amoxicillin group. The intention-to-treat analysis gave similar clinical results. Tolerability was good in both groups. The efficacy and safety of amoxicillin 1 g b.i.d. for 6 days were not statistically different from those of penicillin V 1 MU t.i.d. for 10 days in the treatment of streptococcal tonsillitis in adults.