The penetration activity of cefamandole into different human tissues was studied under experimental conditions. The authors obtained samples of corticalis, spongiosa, cutis, subcutis, fascia and muscle during surgery in 42 cases. Cefamandole was given i.v. by means of: 1. single injections of 40 mg/kg body weight. 2. multiple injections with an initial dose of 40 mg/kg body weight and reinjections of 20 mg/kg body weight after reaching half-life, 3. permanent infusions of 50 mg/kg body weight per hour during 70 min. The investigation is based upon 482 serum level and 330 tissue level determinations. In case of tissue levels the extra- and intravascular concentrations had to be separated so that the contamination of the investigated samples by blood could be quantified. This was done first by the usual way of measuring the hemoglobin concentration, and additionally by the dextran method which was used for control of the hemoglobin method for the first time. The cefamandole conentrations following single and multiple injection did not show any differences in all tissues studied. Distinctly higher concentrations were found after permanent infusions, though with a considerably higher total dose.