Fourier transform infrared (FT-IR) spectroscopy due to its speed and sensitivity is becoming an increasingly powerful tool in the study of cell composition. We outline the potential of FT-IR microspectroscopy in monitoring mitogenic and cell mediated lymphocyte activation. We demonstrate the potential of FT-IR spectroscopy in histocompatibility testing by showing that significant spectral differences (p < 0.001, for the mean integrated intensity of phosphodiester band located in the 1142-996 cm(-1) region) exist between lymphocyte cocultures from pairs of HLA matched and mismatched volunteers after only 90 min of incubation. The preliminary results indicate that early spectral changes measured are due to HLA differences between individuals, although the relative contribution of class I and class II differences has yet to be determined. FT-IR spectroscopy represents a novel approach to histocompatibility matching and the rapidity and sensitivity of the technique indicates a potential role in matching protocols for clinical use, particularly in allogeneic bone marrow transplantation.