The occurrence of subgingival enteric rods, yeasts and staphylococci (pre-treatment and post-treatment) was examined in 21 adult periodontitis patients receiving mechanical periodontal therapy and systemic doxycycline (200 mg on first day, then 100 mg/day for 20 days). Subgingival samples obtained prior to, and 2 weeks and 4 weeks after completion of the antibiotic therapy were transported in VMGA III and plated onto TSBV (for enteric rods and yeasts) and Staphylococcus 110 media. At baseline, small numbers of enteric rods (3 patients), yeasts (5 patients) and staphylococci (11 patients) were detected subgingivally. After the antibiotic therapy, more than 10-fold increases were seen in subgingival numbers of Enterobacter aerogenes (2 patients), Escherichia coli (1 patient), Candida albicans (2 patients), and staphylococci (11 patients). These findings demonstrating that systemic doxycycline therapy may result in at least temporary subgingival overgrowths of enteric rods, yeasts and staphylococci, may indicate the risk of frequent use of tetracycline in periodontal therapy.