This article has attempted to show that killing of, or damage to, lymphocytes by cancer chemotherapeutic agents does not necessarily lead to immunosuppression, but can just as readily result in immunopotentiation. Although this concept is widely accepted by experimental immunologists, it is not yet fully appreciated by clinical immunologists and clinicians who study cytotoxic agents. The data accumulated so far suggest that for the most extensively studied drug, CY, the most important variable determining whether one observes immunosuppression or immunopotentiation is the timing of the administration of CY and antigen. In animal system, immunopotentiation is produced by administering CY one to four days before antigens, while administration of CY after antigen generally results in immunosuppression. Although in our own studies immunopotentiation was achieved in patients by giving CY three days before antigen, we did not determine whether this interval was optimal, and further clinical study of this variable is needed. The dose of CY is probably less important than the timing. It is premature to speculate on the potential usefulness of CY and other cytotoxic drugs in augmenting immunity to clinically important antigens in patients with cancer or other disease states associated with immunosuppression. However, it is clear that the realization that cytotoxic drugs can be immunopotentiating has given a new perspective on immunoregulation. At the very least, these drugs will be valuable tools in the study of human immune responsiveness and the factors that modulate it.