Polyethylene glycol was attached covalently to adenosine deaminase (ADA) using cyanuric chloride as the coupling agent. The modified adenosine deaminase (PEG-ADA) appears to lose its immunogenicity in mice following multiple intravenous injections. PEG-ADA does not react with antibodies raised against native ADA. The circulating half-life (T1/2) of PEG-ADA was increased to 28 hr. The lack of detectable antibody formation and long circulating life may make PEG-ADA suitable for treating human ADA deficiency.