Streptokinase is a strongly antigenic bacterial protein. So, freedom from antigenicity is particularly important in the event where retreatment with the streptokinase is required at > 2 weeks after the initial medication. The failure to meet this criterion is perhaps the greatest disadvantage associated with streptokinase. In [3-51 conjugation of polyethylene glycol, a non-immunogenic polymer, to albumin, catalase or L-asparaginase leads to a complete loss of its antigenicity with retention of its enzymic activity. We modified the streptokinase with polyethylene glycol (M, 5000) and tried to see the effect of the modification on the reduction of the antigenic reactivity of the streptokinase towards anti-streptokinase serum. We aimed to obtain preparations that could be administered intravenously as a safety anti-thrombic drug. Streptokinase was modified as in [3]; monomethoxypolyethylene glycol (9 mmol) was coupled with cyanic chloride (2.7 mmol) to form 2-0methoxypolyethylene glycol-4,6-dichloro-S-triazine, activated polyethylene glycol. To a streptokinase solution (50 mg) in 0.1 M borate buffer (pH 9.2) activated 5000 M, polyethylene glycol was added. The mixture was incubated for 1 h at 4°C then filtered with an ultrafiltration apparatus with XM-50 membrane to remove free activated polyethylene glycol. The modified streptokinase were synthesized by changing the molar ratio of activated polyethylene glycol (PEG) to amino groups in streptokinase molecule (PEG/-NH2: 0.5, 0.8, 1.0 and 3.0). The total amino groups in the streptokinase molecule are 34, including c-amino group in lysine residues and 1 terminal amino group [6]. The degree of modification of amino groups in the molecule were determined by measuring the amount of free amino groups with trinitrobenzene sulfonate [7]. Protein concentrations were determined using an extinction coefficient, EiE at 278 nm of 19.4 [S]. Here, we describe the modified streptokinase with a complete loss of its antigenicity and with retention of its activity.