A review.The half-lives of proteins in vivo can be increased by covalently attaching the polymer polyethylene glycol (PEG) to them.This can significantly decrease their rate of clearance from plasma.The clearance rate is inversely proportional to the total mol. weight of the construct.This approach has been used to design cytokine constructs that can be administered once a week, rather than on a daily or every other day schedule.Two cytokines for which this approach appears to be successful are PEG-interferon-α2a (PEG-IFN-α2a; Pegasys) and PEG-granulocyte colony-stimulating factor (PEG-G-CSF; SD/01).Both use large MW PEG (20-40 kDa) to give sufficiently long duration in vivo.With PEG-G-CSF conjugates, the in vivo efficacy is directly proportional to mol. weight, whereas the in vitro activity is inversely proportional, suggestion that overall duration of contact is more important than affinity of the interaction.Conjugates of a number of other cytokines have been prepared, but until recently, few have used the large mol. weight polymers.As this approach is likely to be taken in the future to make new PEG-cytokine constructs, thorough in vivo pharmacokinetic studies will be essential for their development and clin. use.