Trans-Dehydrocrotonin, a 19-nor-clerodane, is the major norditerpene obtained from Croton cajucara, a Brazilian medicinal plant which presents important biological effects, such as antineoplastic and antiulcerogenic activities. In this work, we analyzed the effect of this sesquiterpene lactone on normal human lymphocytes. The cell viability was verified after treatment for 24 and 72 h with trans-dehydrocrotonin, in the presence and absence of phytohemagglutin (specific mitogen for this cell), through three endpoints to assess cytotoxicity in vitro: MTT reduction (mitochondrial function), protein quantification (cell number) and phosphatase activity (cell metabolism). When the cells were treated with dehydrocrotonin in the presence of mitogen, no toxic effect was observed. Nevertheless, in the absence of mitogen, the IC50 was 450 μM for MTT reduction and phosphatase activity. Moreover, in this condition, trans-dehydrocrotonin caused stimulation of protein content from 100 μM. Our results suggest that phytohemagglutin protects human lymphocytes against the trans-dehydrocrotonin toxic effect.