Widespread use of antibiotics has raised fears that increased numbers of bacteria will become resistant thereby diminishing the overall ability of antibiotics to control infection. While many investigations have shown that resistance to a particular antibiotic increases during the time that the antibiotic is being used, few studies have examined if the increased numbers of antibiotic resistant bacteria persist subsequent to cessation of antibiotic use. In this study we sought to determine if the erythromycin-resistant (ER) staphylococci that emerge subsequent to application of topical E are localized only to the site of application, if ER staphylococci remain at an increased density as compared to baseline density upon cessation of E use, and if ecological disruptions in the cutaneous flora lead to colonization by potential pathogens. A total of 225 subjects were divided into two unbalanced, coded groups consisting of treatment with 2% topical E (n=179) or vehicle (V) only (n=46). To assure compliance, 0.2 gm E or V was applied to the subjects forehead twice a day by lab personnel for a period of 6 weeks. Bacteriological samples were obtained from the forehead, nares and back at baseline, after 6 weeks of treatment, and at 3 and 6 weeks following cessation of treatment. A breakpoint of ≥ 8 ug/ml were used to identify ER staph. The baseline prevalence of ER staph on the forehead and nose was about 80% whereas the back was 50%. The baseline density of ER staph was approximately 20% at all three sites. In contrast to the V group, significant increases in the both prevalence and density of ER staph at three body sites were observed after 6 weeks of E treatment. However, within 6 weeks post-treatment with E, prevalence and density of ER staph returned to baseline values. There was no increase in the prevalence or density of S. aureus, GNR, or yeast at any point in the study nor was there increased resistance to any other antibiotic expect clindamycin. The density of total aerobic organisms also remained static. These data demonstrate that the cutaneous ecological balance is not disrupted by the presence of topical 2% E.