A stable 99mTc-labelled compound that is easy to prepare and that is retained for a long period of time in the blood would constitute an ideal replacement for 99mTc-HSA (limited by its rapid diffusion) and 99mTc-erythrocytes (lengthy and risky in vitro labelling) as tracer agent for ventriculography. We investigated whether 99mTc-labelled polymers would be suitable for this purpose. Four types of poly-L-lysine (PL) (Mw 41,000 to 377,000) were used either in underivatized form labelled at pH 12, or derivatized with a varying number of mercaptoacetyl (MA) substituents by reaction with N-hydroxysuccinimidyl-S-acetylmercaptoacetate followed by deprotection with hydroxylamine and labelling at pH 7.5. A high labelling yield was obtained in all cases. HPLC-purified 99mTc-PLs and 99mTc-MA-PLs were evaluated in mice, with 125I-HSA as an internal biological standard. The retention in the blood at 10 minutes and 60 minutes p.i. was not higher than about 30% for any of the tested compounds versus 84% for 125I-HSA, and was only 10% for the smallest 99mTc-labelled PL and MA-PL. Liver uptake was high for the 99mTc-PLs, whereas the 99mTc-MA-PL's were excreted in significant amounts to the urine. It is concluded that 99mTc-labelled poly-L-lysines or polymercaptoacetyl-poly-L-lysines are not suitable as blood pool tracer agents.