Periareolar nonpuerperal breast infection is a troublesome entity whose treatment is still a matter of debate. Thirty-eight female patients--9 with acute infection and 29 with chronic infection--were prospectively studied over a 3-year period. Sixty isolates were harvested from 50 pus specimens obtained by fine-needle aspiration, with a predominance of staphylococci (23 isolates) and peptostreptococci (18 isolates). On the basis of these findings, an antimicrobial regimen consisting most often of amoxicillin plus clavulanic acid was administered for 6-8 weeks. Simultaneous surgery was required in 13 cases (34.2%). Despite a good response during therapy, 7 (21.9%) of 32 patients relapsed during a follow-up period of < or = 3 years; all 7 patients had presented with chronic infection. We conclude that prolonged therapy with agents active against both staphylococci and anaerobes is essential in periareolar breast infection; in cases with an established fistula, radical surgery (i.e., fistulotomy or fistulectomy) appears inevitable.