The purpose of this study was to determine the effectiveness of the three antimicrobials--Minocycline HCI, Erythromycin and Ampicillin based on the percentage reduction of bacteria present in subgingival microflora and in vitro assessment of antibiotic susceptibility of cultured strains of predominant microorganisms present in a diseased periodontium. Twelve volunteers 18 to 65 years of age, with moderate to severe periodontal disease, were randomly divided into Group A and Group B of 6 members each. Oral lavage procedure was performed to Group A and Group B received systemic administration of antibiotic for five days. Patients 1 & 2, 3 & 4 and 5 & 6 received minocycline HCI, Erythromycin and Ampicillin respectively. Microbiologic samples in the subgingival crevicular area in selected tooth exhibiting clinical periodontal breakdown were obtained from all the subjects prior to and after the oral lavage procedure and systemic drug administration. Streptococcus viridans is the most predominant aerobic microorganism obtained from 83% of samples. However no anaerobic microorganism has been isolated. Bacterial sensitivity testing showed 60% of samples with positive growth of microorganisms (S. viridans) were also equally sensitive to Minocycline HCI, Erythromycin and Ampicillin. Oral lavage proved to be ineffective in reducing the number of bacteria. However, systemic drug administration revealed that there was a reduction in bacterial count after taking such antibiotics for five days which is more favorable to Minocycline HCI.