The disposition of cefonicid (2 g intravenously every 24 h) was assessed in 15 patients with skin and skin structure infections. Trough and peak concentrations in serum were measured on two successive days to verify the attainment of steady state; and 1 trough and 12 postdose values of the concentration in serum were collected on the following day. Cefonicid concentrations in serum were determined by high-performance liquid chromatography. The cefonicid serum concentration versus time profile after intravenous infusion was clearly biexponential in all patients. The terminal elimination half-life determined by nonlinear regression analysis was 4.63 ± 14.9 h (mean ± standard deviation). The steady-state volume of distribution and total body clearance were 0.12 ± 0.04 liter/kg and 0.369 ± 0.110 ml/min per kg, respectively. These results are comparable to parameters derived from previous studies in noninfected normal volunteers. Thus, the disposition of cefonicid is not altered in patients with severe skin structure infections.