Limiting dilution analysis (LDA) provides a practical and simple method for determining the frequency of defined clones of lymphocytes responding to a specific antigen or with a particular effector function. The importance of the technique stems from the fact that it is the only way to assess the immune response in humans, at the level of the cell, in a quantitative manner. In this article Claire Sharrock, Edward Kaminski and Stephen Man review the current status of the technique and its applications in human immunology.