Summary:The study objective was to evaluate serum, peritoneal fluid, and appendix tissue concentrations of clindamycin using two differing clindamycin regimens. Patients age 16 years and older who were about to undergo appendectomies were randomly assigned to receive gentamicin 1.5 mg/kg every 8 h admixed with clindamycin 900 mg every 8 h (8‐h group) or clindamycin 600 mg every 6 h given separately (6‐h group). Doses of each regimen were given preoperatively. Serum, peritoneal fluid, and appendix tissue samples were obtained intraoperatively, and frozen at −70°C for gas chromatographic drug analysis. Twenty‐one patients were evaluated, 11 patients in the 8‐h group and 10 patients in the 6‐h group. Values are reported as means ± standard deviations. The values in the 8‐h group were 12.3 ± 14.1 &mgr;g/ml, 8.7 ± 3.9 &mgr;g/ml, and 9.8 ± 10.3 &mgr;g/g for serum, peritoneal fluid, and appendix tissue, respectively. The values in the 6‐h group were 9.7 ± 5.1 &mgr;g/ml, 5.8 ± 5.3 &mgr;g/ml, and 6.2 ± 4.9 &mgr;g/g for serum, peritoneal fluid, and appendix tissue, respectively. The 6‐h group received more doses preoperatively (1.8 ± 0.6) than the 8‐h group (1.2 ± 0.4; p < 0.05). No differences in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue for the 8‐h group and the 6‐h group were noted. The study revealed a similarity in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue using either clindamycin 900 mg given by intermittent intravenous infusion every 8 h admixed with gentamicin or clindamycin 600 mg given every 6‐h separately.