In spring, spleen cells (SC) derived from outbred adult snakes, Psammophis sibilans, proliferated vigorously in mixed leucocyte cultures (MLC), thus indicating that reptiles are endowed with the subset(s) of lymphocytes capable of recognizing and responding to alloantigens. Sephadex G-10- or nylon wool-adherent latex-ingesting cells provided accessory, rather than stimulatory, function in MLC. The data, based on numerous one- and two-way MLR studies, showed that the snake P. sibilans possesses strong lymphocyte-activating determinants (LAD) which, however, appeared not to be extensively diverse, as mutually or unilaterally unresponsive SC combinations were quite often observed. Furthermore, seasonal investigations revealed that the lymphoproliferative response in MLR is considerable only in some months of spring and autumn, being abrogated during the rest of the year. These findings suggest that antigen sharing and environmental conditions greatly restrict the cell-mediated immune potential of snakes.