Concanavalin A. (Con A)2 and other plant lectins have recently been extensively employed as biochemical probes in order to investigate cell surfaces and specific binding sites on these surfaces (1–3). Con A is also a potent lymphocyte mitogen (4, 5). In the course of comparative investigations of the mitogenic property of Con A and bacterial mitogens, we found Con A preparations to be pyrogenic. Pyrogenicity of Con A had previously been reported (6); however, the febrile response in American Dutch rabbits we observed was strikingly similar to the biphasic curves obtained upon i.v. injection of Gram-negative bacterial endotoxin (lipopolysaccharide). Moreover, by using dose response relationships of several Con A preparations observed in rabbit pyrogen tests, the pyrogenic activity could be biologically quantitated, as reported for endotoxin (7). An amount necessary for a minimal pyrogenic dose at 3 hr (MPD-3) could thus be determined (7). We therefore felt compelled to investigate further any possible cross-reactive relationships between the Con A preparations and endotoxin.