In this paper, we emphasize the rationale and work-up studies for using two radiolabelled anti-lymphocyte monoclonal antibodies for in vivo application as radiolabelling agents for T and B cells. In vitro experimental work involved radioimmunoassays on human lymphoid cell lines and anticoagulated whole blood with identification of relevant binding kinetics in terms of antibody internalization and elution. We tested also for the effect of the radiolabelled monoclonal antibodies on in vitro cell function defined as mitogen-induced proliferation in whole blood. As a final work-up in an animal model, the distribution of both unlabelled and 111In-labelled anti-Pan T cell monoclonal antibody was studied in the rat. Results from the in vitro experiments pointed to the possibility of using the described technique for specific lymphocyte radiolabelling. The in vivo application enabled us to identify optimal doses of antibody and radioactivity which showed agreement with the in vitro data.