The effects of human fibrinogen and Cl- on the activation of native human plasminogen by streptokinase, at 37 degrees C, in isotonic buffers, consisting of 10 mM Hepes-NaOH, 150 mM NaOAc-NaCl, pH 7.4, have been examined. We find that Cl- acts as a mixed-type inhibitor of plasminogen activation, with a Ki in the range of 6.4-9.2 mM, in the absence and presence (1.0 microM) of fibrinogen. Fibrinogen displays an effect on plasminogen activation kinetics consistent with its function as a mixed-type nonessential activator, with Ka values between 110 and 240 nM, in the absence and presence (50 mM) of Cl-. These observations suggest opposing roles for fibrinogen and Cl- in regulating plasminogen activation.