Free and total concentrations of cefazolin were compared in plasma and interstitial fluid during continuous intravenous infusion therapy. Seven patients, median age 53 (25-74) years, were administered a constant infusion of cefazolin at a mean (+/-S.D.) dose of 3.5 g (+/-1.1) per 24 h for > or = 5 days. Four blisters were induced on the forearm of each patient for sampling of interstitial fluid. Free concentrations in plasma and interstitial fluid were similar, and correlated better than total concentrations (r(2) = 0.82, P = 0.005 versus r(2) = 0.54, P = 0.056). In all patients, the free concentrations in the interstitial fluid were at least two-fold the MIC(90) for Staphylococcus aureus.