The inability to measure the effects of immunosuppressive drugs on immune c
ells in vivo has always severely limited preclinical drug development, the
design and interpretation of clinical trials and the optimal clinical use o
f this drug class in transplantation. Now, new technologies using microlite
r samples of whole blood and exploiting the specificity, sensitivity and ve
rsatility of flow cytometry have been developed. These novel techniques not
only are illuminating the 'black box' that has obscured the pharmacodynami
c effects of immunosuppressants but also are uncovering new mechanisms of a
ction of these drugs. Pharmacodynamic assays measure biologically relevant
events in vivo, since changes in lymphocyte functions in blood collected fr
om immunosuppressed graft recipients faithfully reflect histopathologic eve
nts within allograft tissue.