The chance isolation of a mouse strain mutant that shows a complete deficiency in both the humoral and cellular immunity compartments has opened new perspectives in numerous fields of medicine and biology, including oncology, hematology and immunology. However, the original concept that the severe combined immunodeficiency mouse might behave as a 'living vessel', and allow experimental approaches that are precluded in man by technical and ethical constraints, has not fully withstood the test of time. At present, despite the body of important results achieved in the past few years, the use of this model in some areas is somewhat deregulated; no standard protocols are available, and some critical variables that could affect experimental results are not always under control. In this article, we have focused on the use of the SCID mouse reconstituted with human mature lymphoid cells in immunological studies, and tried to enucleate, in the array of existing experimental work, some basic concepts that might favor more judicious and appropriate approaches to the use of this important experimental model.